The engineered nanoparticles are effectively used for cancer treatment due to their targeted drug delivery approach. Download the Aranca report on Technology and Patent Research for current research trends and developments.
Targeted Drug Delivery System Using NanoparticlesSelf
Targeted drug delivery, also known as smart drug delivery, is a method of treatment that involves the increase in medicament in one or few body parts in comparison to others.
This presentation which highlights the various technology innovations and developments in targeted drug delivery as well as maps its applications in different therapeutic segments was presented at the Novel Drug Delivery Systems and Clinical Trial Management 2013 Conference at Shangai, China.
Nanotechnology and potential in Cancer therapy and treatmentladen12
this presentation focuses on new nanotechnology and it possible use in detection and therapy with cancer. it was prepared by final year biochemistry student at NCU.
New science is redefining cancer as a large number of narrowly defined diseases and bringing therapeutic options to an expanded number of patients. With the rapid growth in the oncology treatment landscape, health systems are struggling to adapt and embrace the evolution—including regulatory systems, diagnostic infrastructure, treatment providers and financing mechanisms. These challenges will require urgent attention in light of the strong near-term pipeline of clinically distinctive therapies and new programs that are galvanizing research efforts to change the trajectory for cancer.
Read the full report >> http://imsh.co/2axszmt
Targeted Drug Delivery System Using NanoparticlesSelf
Targeted drug delivery, also known as smart drug delivery, is a method of treatment that involves the increase in medicament in one or few body parts in comparison to others.
This presentation which highlights the various technology innovations and developments in targeted drug delivery as well as maps its applications in different therapeutic segments was presented at the Novel Drug Delivery Systems and Clinical Trial Management 2013 Conference at Shangai, China.
Nanotechnology and potential in Cancer therapy and treatmentladen12
this presentation focuses on new nanotechnology and it possible use in detection and therapy with cancer. it was prepared by final year biochemistry student at NCU.
New science is redefining cancer as a large number of narrowly defined diseases and bringing therapeutic options to an expanded number of patients. With the rapid growth in the oncology treatment landscape, health systems are struggling to adapt and embrace the evolution—including regulatory systems, diagnostic infrastructure, treatment providers and financing mechanisms. These challenges will require urgent attention in light of the strong near-term pipeline of clinically distinctive therapies and new programs that are galvanizing research efforts to change the trajectory for cancer.
Read the full report >> http://imsh.co/2axszmt
The field of nanotechnology was first Discovered by Professor Richard P. Feynman in 1959 (Nobel laureate in physics, 1965) [2]. Nanotechnology is the science of the small; very small and it is used for the management of substance at a small scale. At this size, molecules and atoms work in a different way, and provide a variety of unpredicted and attractive uses .
Nanotechnology for cancer therapy recent developmentsroshan telrandhe
This paper is an overview of advances and prospects in applications of nanotechnology for cancer treatment. Nanotechnology is an use for prevention, diagnosis, and treatment. nanotechnology offers a promise for the targeted delivery of drugs, genes and protein to tumer tissue and therefore alleviating the toxicity of anticancer agent in healthy tissues. Cancer is one of the leading causes of death worldwide. Nanotechnology is one of the most rapidly growing fields in the 21st centuryThese mainly include arrays of nanocantilevers, nanotubes and nanowires for multiplexing detection, multifunctional injectable nanovectors for therapeutics and diagnostics. This article review current nanotechnology platforms for anticancer drug delivery, including polymeric nanoparticles, liposomes, dendrimers, nanoshells, nuclear acid base nanoparticle [DNA, RNA interference (RNAi), and antisense oligonucleotide (ASO) ] The review increases awarnes of advantages in cancer therapy
A General Overview of Nano Medicine-Efficacy in Therapeutic Science and Curre...Berklin
Nanotechnology’s introduction has dramatically improved a number of scientific fields, one of which is medicinal research. Nanomedicine is aimed to offer healthcare medications and chemicals a new dimension. The small size of nanoparticles, permits them to circulate in the body without interrupting oxygenation and escape filtration by both the renal and gastrointestinal networks. These are the few properties that distinguish them apart from traditional therapeutic procedures. The increased permeability and durability effect result in successful penetration inside the tumor tissues, providing cancer treatment a new lease on life. Efficient transportation pathways, on the other hand, produce genotoxicity and mutagenicity by interacting with genes that are essential for smooth functioning. As the specific interactions of nanomedicines with biological systems are still unknown, comprehending nanomedicines' toxicological effects is tough. The lack of regulatory direction in this field remains a research gap that we would want to examine in this study.
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Despite remarkable scientific and technological achievements during the 20th century, the 21st century has already witnessed additional new and profound changes in all areas of medical science and research, including innovations and discoveries in biology, cellular biology, genomics and proteomics, pharmaceuticals, medical devices, and information technology. This review is an up-date on some of the existing therapies, drug delivery technologies, and approaches that aimed to improve patients’ health care and quality of their life.
A General Overview of Nano Medicine-Efficacy in Therapeutic Science and Curre...ceijjournals
Nanotechnology’s introduction has dramatically improved a number of scientific fields, one of which is
medicinal research. Nanomedicine is aimed to offer healthcare medications and chemicals a new
dimension. The small size of nanoparticles, permits them to circulate in the body without interrupting
oxygenation and escape filtration by both the renal and gastrointestinal networks. These are the few
properties that distinguish them apart from traditional therapeutic procedures. The increased permeability
and durability effect result in successful penetration inside the tumor tissues, providing cancer treatment a
new lease on life. Efficient transportation pathways, on the other hand, produce genotoxicity and
mutagenicity by interacting with genes that are essential for smooth functioning. As the specific
interactions of nanomedicines with biological systems are still unknown, comprehending nanomedicines'
toxicological effects is tough. The lack of regulatory direction in this field remains a research gap that we
would want to examine in this study.
Presentation on Nanoparticles Smart Drug Delivery System For Cancer no company
Nano technology is a rapidly expanding field, encompassing the development of a man-made materials in 5-200 nanometer size range. This dimension vastly exceeds that of standard organic molecules.
Please contact us if you want our services.(We work on every kind of Thesis Presentations (Word, Power point, Excel, Adobe photoshop and Auto-cad).
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An Overview of Active and Passive Targeting Strategies to Improve the Nano-Ca...NoorulainMehmood1
The efficient delivery of therapeutic agents to tumor sites remains a significant challenge in cancer treatment. Nano-carriers have emerged as promising vehicles for targeted drug delivery due to their ability to enhance drug solubility, prolong circulation time, and minimize systemic toxicity. This review provides a comprehensive overview of active and passive targeting strategies employed to improve the efficiency of nano-carriers in reaching and accumulating at tumor sites. Active targeting utilizes ligands or antibodies to specifically bind to receptors overexpressed on tumor cells, while passive targeting exploits the unique characteristics of the tumor microenvironment, such as leaky vasculature and impaired lymphatic drainage, to enhance accumulation. The synergistic combination of active and passive targeting strategies holds great potential for optimizing drug delivery to tumors while minimizing off-target effects. In-depth understanding of these strategies is crucial for the rational design and development of nano-carriers tailored for enhanced efficacy in cancer therapy.
Keywords: Nano-carriers, tumor targeting, active targeting, passive targeting, drug delivery, cancer therapy
The French Animal Healthcare Market is on the upswing boosted by growing disposable income, a rising number of pets, growing animal healthcare awareness, etc.Get detailed Business Analysis Infographic from Aranca.
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State of ICS and IoT Cyber Threat Landscape Report 2024 previewPrayukth K V
The IoT and OT threat landscape report has been prepared by the Threat Research Team at Sectrio using data from Sectrio, cyber threat intelligence farming facilities spread across over 85 cities around the world. In addition, Sectrio also runs AI-based advanced threat and payload engagement facilities that serve as sinks to attract and engage sophisticated threat actors, and newer malware including new variants and latent threats that are at an earlier stage of development.
The latest edition of the OT/ICS and IoT security Threat Landscape Report 2024 also covers:
State of global ICS asset and network exposure
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Global APT activity, AI usage, actor and tactic profiles, and implications
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Major cyber events in 2024
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Cyberattack types and targets
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In-depth analysis of the cyber threat landscape across North America, South America, Europe, APAC, and the Middle East
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Cyber risk predictions
Axis of attacks – Europe
Systemic attacks in the Middle East
Download the full report from here:
https://sectrio.com/resources/ot-threat-landscape-reports/sectrio-releases-ot-ics-and-iot-security-threat-landscape-report-2024/
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In today's fast-changing business world, Companies that adapt and embrace new ideas often need help to keep up with the competition. However, fostering a culture of innovation takes much work. It takes vision, leadership and willingness to take risks in the right proportion. Sachin Dev Duggal, co-founder of Builder.ai, has perfected the art of this balance, creating a company culture where creativity and growth are nurtured at each stage.
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As AI technology is pushing into IT I was wondering myself, as an “infrastructure container kubernetes guy”, how get this fancy AI technology get managed from an infrastructure operational view? Is it possible to apply our lovely cloud native principals as well? What benefit’s both technologies could bring to each other?
Let me take this questions and provide you a short journey through existing deployment models and use cases for AI software. On practical examples, we discuss what cloud/on-premise strategy we may need for applying it to our own infrastructure to get it to work from an enterprise perspective. I want to give an overview about infrastructure requirements and technologies, what could be beneficial or limiting your AI use cases in an enterprise environment. An interactive Demo will give you some insides, what approaches I got already working for real.
UiPath Test Automation using UiPath Test Suite series, part 3DianaGray10
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UI automation Introduction,
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Pradeep Chinnala, Senior Consultant Automation Developer @WonderBotz and UiPath MVP
Deepak Rai, Automation Practice Lead, Boundaryless Group and UiPath MVP
Essentials of Automations: Optimizing FME Workflows with ParametersSafe Software
Are you looking to streamline your workflows and boost your projects’ efficiency? Do you find yourself searching for ways to add flexibility and control over your FME workflows? If so, you’re in the right place.
Join us for an insightful dive into the world of FME parameters, a critical element in optimizing workflow efficiency. This webinar marks the beginning of our three-part “Essentials of Automation” series. This first webinar is designed to equip you with the knowledge and skills to utilize parameters effectively: enhancing the flexibility, maintainability, and user control of your FME projects.
Here’s what you’ll gain:
- Essentials of FME Parameters: Understand the pivotal role of parameters, including Reader/Writer, Transformer, User, and FME Flow categories. Discover how they are the key to unlocking automation and optimization within your workflows.
- Practical Applications in FME Form: Delve into key user parameter types including choice, connections, and file URLs. Allow users to control how a workflow runs, making your workflows more reusable. Learn to import values and deliver the best user experience for your workflows while enhancing accuracy.
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We’ll wrap up with a glimpse into future webinars, followed by a Q&A session to address your specific questions surrounding this topic.
Don’t miss this opportunity to elevate your FME expertise and drive your projects to new heights of efficiency.
Key Trends Shaping the Future of Infrastructure.pdfCheryl Hung
Keynote at DIGIT West Expo, Glasgow on 29 May 2024.
Cheryl Hung, ochery.com
Sr Director, Infrastructure Ecosystem, Arm.
The key trends across hardware, cloud and open-source; exploring how these areas are likely to mature and develop over the short and long-term, and then considering how organisations can position themselves to adapt and thrive.
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Sidekick Solutions uses Bonterra Impact Management (fka Social Solutions Apricot) and automation solutions to integrate data for business workflows.
We believe integration and automation are essential to user experience and the promise of efficient work through technology. Automation is the critical ingredient to realizing that full vision. We develop integration products and services for Bonterra Case Management software to support the deployment of automations for a variety of use cases.
This video focuses on the notifications, alerts, and approval requests using Slack for Bonterra Impact Management. The solutions covered in this webinar can also be deployed for Microsoft Teams.
Interested in deploying notification automations for Bonterra Impact Management? Contact us at sales@sidekicksolutionsllc.com to discuss next steps.
Transcript: Selling digital books in 2024: Insights from industry leaders - T...BookNet Canada
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Link to video recording: https://bnctechforum.ca/sessions/selling-digital-books-in-2024-insights-from-industry-leaders/
Presented by BookNet Canada on May 28, 2024, with support from the Department of Canadian Heritage.
2. 2
TABLE OF CONTENT
1. BACKGROUND OF THE DOMAIN 3
2. UNMET NEEDS OF CONVENTIONAL DOSAGE 5
3. POTENTIAL DRIVERS 6
4. CURRENT RESEARCH 7
5. OUTLOOK 16
3. 3
Nanotechnology is a rapidly evolving domain, as it solves various
issues associated with conventional drug therapeutics, including poor
water solubility, lack of targeting capability, non-specific distribution,
systemic toxicity and low therapeutic index. Nanoparticles are 1–100
nanometres in size. These particles can be used in a targeted drug
delivery approach, as they can specifically target a drug or drug
carrier to minimise drug-originated systemic toxic effects. In addition,
nanoparticles are designed to assist therapeutic agents to pass
through biologic barriers, mediate molecular interactions and identify
molecular changes. After nanoparticles bind with the receptors, they
rapidly undergo receptor-mediated endocytosis or phagocytosis
by cells, releasing the encapsulated drug inside the cell cytoplasm.
Nanoparticles were developed in the late 1960s. During the 1970s,
the first nanoparticle drug delivery system, lipid vesicle, was developed.
In 1983, the US FDA approved the first micellar drug, Sandimmune®,
for systemic administration of nanoparticles in humans. In 1990, the first
polymer–drug nanoconjugate Adagen® was clinically approved
for human use.
Polymeric micelles Liposomes Biodegradable/
biocompatible
nanoparticles
Nanoparticle drug
carriers
Dendrimers
Nanospheres,
nanocapsules,
nanotubes
Metal
nanoparticles
Artificial DNA
nanostructures
Carbon
nanoparticles
Magnetic
nanoparticles
Drug nanoparticle
conjugates
Nanocomposites
Stimuli-based drug
releasing
nanoparticles
Targeting ligand
-modified
nanoparticles
Silica nanoparticles
BACKGROUND OF THE DOMAIN
Protein–drug
nanoconjugates
Types of Nanoparticles
4. 4
Nanoparticles target tumour cells in two ways: active and passive.
• Passive targeting: This term refers to the accumulation of the
drug in areas around the tumour with leaky vasculature; it also
known as the enhanced permeation and retention (EPR) effect.
• Active targeting: This term refers to specific interactions
between the drug/drug carrier and target cells, usually through
specific ligand receptor interactions or antibody-antigen
recognition, for intracellular localisation of the drug.
The EPR effect, a unique characteristic of tumour cells, enables targeted
delivery of anticancer agents. Passive targeting is based primarily on size; the
nanoparticle surface may be modified with several ligands that would interact
with specific receptors over-expressed on the surface of the tumour cells, thus
imparting specificity for active targeting.
Nanoparticles have promising applications in diagnostic, therapeutic and drug
delivery systems for cancer, as they can enter the tissues at the molecular
level; these particles have given platforms for cancer therapy and diagnostics.
Nanoparticles provide a new mode for cancer drug delivery as a carrier
for entry through fenestrations in tumour vasculature, allowing direct cell
access. The modified nanoparticles allow binding to cancer cell membranes,
microenvironment, or cytoplasmic or nuclear receptor sites. This initiates the
delivery of high drug concentrations to the targeted cancer cell with reduced
toxicity of normal tissues. Over the past several decades, the development
and application of engineered nanoparticles to more effectively treat cancer
have witnessed significant advancement.
MECHANISM OF TARGETING
Fig.1. Active and passive targeting by nanoparticles
Source: Kumar Bishwajit Sutradhar and Md. Lutful Amin,
“Nanotechnology in Cancer Drug Delivery and Selective
Targeting,” ISRN Nanotechnology, vol. 2014, Article ID
939378, 12 pages, 2014. doi:10.1155/2014/93937
5. 5
THE CONVENTIONAL DRUG
DELIVERY SYSTEM HAS THE
FOLLOWING DISADVANTAGES:
1. Drug resistance
2. Lack of selectivity
3. Lack of drug solubility
4. Dynamic changes of cancer cells
5. Serious side effects of chemotherapy
6. Poor targeting of heterogenic tumours
7. Small amount of drug reaches the
cancer cells
8. Nonspecific targeting of conventional
delivery
9. Inability of the drug to enter the
core of tumours, resulting in impaired
treatment with reduced dose and
low survival rate
ADVANTAGES OF
NANOPARTICLES:
1. Entry into tissues at the molecular
level
2. Increased drug localisation and cellular
uptake
3. Cancer diagnosis and treatment
applications
4. Feasibility to programme nanoparticles
for recognising cancerous cells
5. Selective and accurate drug delivery,
and avoiding interaction with healthy cells
6. Direct and selective targeting of the drug
to cancerous cells (both active and passive
targeting)
7. Larger surface area with modifiable optical,
electronic, magnetic and biologic properties vis-à vis
macroparticles
8. Assisting therapeutic agents to pass through
biologic barriers, mediate molecular interactions and
identify molecular changes
UNMET NEEDS OF CONVENTIONAL DOSAGE
6. 6
FACTORS DRIVING NANOPARTICLE-BASED CANCER
DRUG DELIVERY SYSTEMS
Efficient
encapsulation
of drugs
Reduces the
effect on non-
target tissues
Lowers volume
of distribution of
the drug
Likely to
overcome drug
resistance
Successful
release of the
drug
Reduces drug
clearance rates
Biocompatibility
Prevents tissue
damage through
regulated drug
release
Successful
delivery of the
drug to the
targeted region of
the body
Improves
pharmacokinetics
and biodistribution
of the drug
Delivers unstable
molecules (proteins,
siRNA and DNA) using
liposomes and polymeric
nanoparticles
Delivers to difficult
sites (brain,
retina, tumours
and intracellular
organelles)
Delivers drugs with
serious side effects
(such as anticancer
agents)
Exhibits the EPR effect,
a unique property
of nanoparticles to
accumulate and interact
with tumour cells
Encapsulation or
conjugation of small
biomolecules such as
proteins, enzymes,
carboxylic acid, DNA
and amino acids
Ability to locate and
specifically target
deep-seated tissues
and organs
7. 7
CURRENT RESEARCH
Nanoparticles have been modified and enhanced to enable the delivery of
drugs across the blood–brain barrier (BBB) as well as improved upon to create
polyethylene glycol (PEG) modified (PEGylated) nanoparticles with a prolonged
blood circulation time. Targeting ligands (such as small organic molecules,
peptides, antibodies and nucleic acids) have been added to the surface of
nanoparticles to specifically target cancerous cells by selectively binding to the
receptors over-expressed on their surface. Furthermore, site-specific release of
a drug contained in a nanoparticulate system by applying an external stimulus,
such as hyperthermia, to a thermosensitive device is another innovative
strategy to achieve targeted delivery. Moreover, multiple types of therapeutic
drugs and/or diagnostic agents (such as contrast agents) could be delivered
using the same carrier to enable combination therapy to overcome multidrug
resistance and achieve real-time determination of treatment efficacy.
8. 8
Polymer nanoparticles are prepared using biodegradable polymers such as
poly(D,L-lactic acid) (PLA) and poly(D,L-lactic-co-glycolic acid) (PLGA). Such
nanoparticles can be used to encapsulate the drug in a polymer coating.
In addition, targeted polymer nanoparticles can be used to deliver drugs to
tumour cells with greater efficacy and reduced cytotoxicity on healthy tissues.
Various drug-encapsulated polymer nanoparticles are formulated using
biocompatible and biodegradable polymers.
Jeremiah A. Johnson and co-
workers of Massachusetts Institute
of Technology, US, developed a
novel polymer nanoparticle drug
delivery system (J. Am. Chem. Soc.
2014, DOI: 10.1021/ja502011g).
They developed the first polymer
nanoparticles that carry a precise
ratio of three cancer drugs
(doxorubicin, camptothecin and
cisplatin) and release them with
three independent release mechanisms. These triple-threat nanoparticles
get rid of ovarian cancer cells better than nanoparticles that utilise either one
or two medications. The design of nanoparticles allows modification to add
more drugs. This approach could lead to new methods of delivering specific
amounts of multiple drugs to patients and could help researchers optimise
doses of such combination therapies. Currently, studies are being conducted
on mice for triple-threat nanoparticles. In addition, Johnson and his co-workers
are testing four-drug combinations as well as co-administering nanoparticles
and therapeutic small-interfering RNAs.
The new technique of drug-polymer blending allows attaching drug molecules
to the polymer’s individual units like pendants before these units assemble into
a polymer nanoparticle (for instance, nanoparticles with hydrophobic docetaxel
and hydrophilic cisplatin). After loading the drugs on the nanoparticle, a ligand
is added that binds to a molecule present on the surfaces of most prostate
cancer cells. This ligand allows these nanoparticles to bypass healthy tissues
and reduce the side effects caused by most chemotherapy drugs. Thus, the
drugs are directly delivered to the target region.
New MIT nanoparticles consist of polymer
chains (blue) and three different drug molecules:
doxorubicin (red), camptothecin (small green
particles) and cisplatin (larger green core).
Source: Jeremiah A. Johnson et.al, A
Convergent Synthetic Platform for Single-
Nanoparticle Combination Cancer Therapy:
Ratiometric Loading and Controlled Release of
Cisplatin, Doxorubicin, and Camptothecin, J.
Am. Chem. Soc. 2014, 136 (16), pp 5896–5899,
DOI: 10.1021/ja502011g
Polymer Nanoparticles
9. 9
Various metal nanoparticles have been tested for selective delivery of drugs
to cancer cells. Of all metallic nanoparticles, gold proved to be the safest and
least toxic agent for drug delivery. Gold nanoparticles (AuNPs) possess several
properties such as inert nature, well-developed synthesis strategies, tunable
size, and flexible and easy surface modification with various chemical and
biological molecules that enhance performance as drug delivery vectors.
AuNPs exhibit a combination of physical, chemical, optical and electronic
properties unique from other biomedical nanoparticles. These properties
enable multifunctional applications such as imaging and diagnosing diseases,
selectively delivering therapeutic agents, sensitising cells and tissues to
treatment regimens, monitoring and guiding surgical procedures, and
preferentially administering electromagnetic radiation to disease sites. AuNPs
show size-dependent optical properties. In general, the intrinsic colour of
nanoparticles changes with size due to surface plasmon resonance. Such
nanoparticles are useful for molecular sensing, diagnostic and imaging
applications. For instance, AuNPs can exhibit different colours based on
size. The drugs coupled to AuNPs help to improve their solubility and uptake
into cancerous tissues. AuNPs can be used to deliver low solubility and
poor pharmacokinetic drugs and imaging agents. Moreover, they can deliver
compounds that are inherently susceptible to enzymatic degradation as well
as those that exhibit poor intracellular penetration (such as siRNA). Gold
nanostructures can simultaneously engage multiple and adjacent receptor
sites, achieving increased selectivity in their uptake. Furthermore, AuNPs are
readily synthesised and modified with chemical and biological molecules,
enhancing their effectiveness for drug delivery and molecular diagnostics.
The current research on AuNPs focuses on AuNPs surface functionalised with
active ligands, allowing optimisation of their binding affinity for a particular
disease type, stage or patient. One of the best methods to deliver a DNA
vaccine is a gene gun using AuNPs, which have been extensively used for
epidermal delivery of DNA vaccines. AuNPs provide the nano-prodrug system
Gold Nanoparticles
10. 10
with reduced size, high loading efficiency, three-dimensional structure and
enhanced cellular uptake capability. Human pilot studies exploring the use of
intravenously administered PEGylated silica–Au core–shell nanoparticles for
NIR laser photothermal ablation of recurrent and/or refractory head and neck
tumours are completed in the US (NCT00848042; Nanospectra Biosciences,
Inc.), with ongoing human pilot studies investigating the use of this technology
for the treatment of primary prostate cancer in Mexico.
The first AuNP therapy that has reached early phase
clinical trials is CYT-6091, 27-nm citrate-coated
AuNPs bound with thiolated PEG and tumour
necrosis factor-α (TNF-α) (Aurimmune; CytImmune
Sciences); this nanoparticle has the dual effect of
increasing tumour targeting and tumour toxicity.
TNF-α is a multifunctional cytokine that is both
cytotoxic and immunomodulatory. The previous
clinical trials of TNF-α demonstrated dose-limiting
toxicities of hypotension and nausea at concentrations of 225 μg m–2, which
limited wide clinical use. Recent preclinical studies compared TNF alone with
citrate AuNP–TNF complexes. The results showed a drastic improvement in
tumour specificity when PEG-thiol was added, with active tumour uptake and a
gradual reduction in liver and spleen concentrations over six hours. Intracellular
AuNPs were detectable in post-treatment tumour biopsies, but not in normal
tissue. A phase I trial of TNF-bound colloidal gold (CYT-6091) was conducted
by intravenously administering these particles in subjects with advanced solid
organ malignancies. This phase I trial (NCT00356980; CytImmune Sciences,
Inc.) was performed to determine the side effects and best dose of TNF-bound
colloidal gold in treating patients with advanced solid tumours. The results of
these phase I clinical trials indicated that PEGylated AuNPs are well tolerated
in humans at therapeutically relevant dosages for TNF-α.
Preclinical studies of CYT-6091 bound with paclitaxel (known to synergise with
TNF) have demonstrated 10 times more paclitaxel uptake in solid tumours than
paclitaxel alone. AuNPs conjugated to chemotherapeutic drugs can overcome
multidrug resistance through increased particle uptake by endocytosis and
subsequent drug release. Cheng and co-workers coupled doxorubicin (DOX)
to 5-nm PEGylated gold nanospheres via an intracellular enzyme-cleavable
disulfide linkage. The results showed that DOX-functionalised nanoparticles
had an increased cellular uptake relative to nanoparticles without DOX, as
well as an increased cytotoxicity towards the multidrug resistance cell line.
Polymer-functionalised (PEGylated) AuNPs can exhibit long circulation times
(nearly 51 hour of blood half life) and can avoid off-target uptake and blood
clearance associated with recognition by the immune system.
Some polymer and ligand-functionalised AuNPs are used for controlled drug
delivery of cancer therapeutics. AuNPs can allow increasingly specific and
accelerated drug delivery that minimises unintended side effects, increases
tolerable dosages and overcomes insensitivity in several treatment-resistant
cell lines.
11. 11
Liposomes are self-assembling, spherical, closed colloidal structures that are
composed of lipid bilayers surrounding an aqueous space. Certain anticancer
drugs, such as doxorubicin (Doxil) and daunorubicin, are provided via
liposomes. Liposomal cisplatin has received an orphan drug designation for
pancreatic cancer from the European Medicines Agency (EMA).
CPX-351 (cytarabine:daunorubicin) liposome injection represents a new
approach to develop combinations of drugs, in which drug molar ratios with
synergistic anti-tumour activity are encapsulated in a drug delivery vehicle to
maintain the desired ratio after administration. The US FDA granted an orphan
drug status to CPX-351 to treat acute myeloid leukaemia (AML). Currently,
CPX-351 is in phase III clinical development for the treatment of AML.
On 20 January 2015, Celator
Pharmaceuticals received the
FDA Fast Track designation
for CPX-351 to treat elderly
patients with secondary AML.
The FDA established the Fast
Track designation process to
facilitate the development and
expedite the review of drugs
intended to treat serious or
life-threatening conditions,
and address an unmet medical
need. On 19 November 2014,
Merrimack Pharmaceuticals announced the FDA granted nanoliposomal
irinotecan injection (MM-398), also known as nal-IRI, the Fast Track
designation to treat patients with metastatic pancreatic adenocarcinoma, who
have been previously treated using the gemcitabine-based therapy. Currently,
Merrimack Pharmaceuticals is preparing a New Drug Application (NDA) for
MM-398 in the US to treat pancreatic cancer.
PX-351 is a liposomal formulation of a synergistic 5:1 molar ratio of cytarabine
and daunorubicin; these two agents are commonly used to treat blood
cancers, particularly AML. CPX-1 (irinotecan:floxuridine) is a liposomal
formulation of a synergistic 1:1 molar ratio of irinotecan HCI and floxuridine,
components of a drug regimen that has proven to be useful in the treatment of
cancer, particularly gastrointestinal (GI) tumours. Both drugs are approved for
the treatment of colorectal cancer. CPX-1 is undergoing phase II clinical trials.
Liposomes
Mushroom regime
(Low PEG density)
Crystalline drug
Hydrophobic drug
Surface - conjugated
drug
Brush regime
(High PED density)
Hydrophilic drug
DNA/RNA/siRNA
Targeting ligand
Protein
Antibody
Peptide
Carbohydrate
Small molecule
3.5nm
4.5nm
12. 12
Due to their ultrafine size, magnetic properties and biocompatibility,
superparamagnetic iron oxide nanoparticles (SPIONPs) have emerged as
promising candidates for various biomedical applications such as:
• Enhanced-resolution contrast agents for MRI
• Targeted drug delivery and imaging
• Hyperthermia
• Gene therapy
• Stem cell tracking
• Molecular/cellular tracking
• Magnetic separation technologies (rapid DNA sequencing)
• Early detection of inflammation, cancer, diabetes and atherosclerosis
To improve cellular uptake, these particles are modified with a peculiar surface
coating, so that they can be easily conjugated to drugs, proteins, enzymes,
antibodies or nucleotides, and can be directed to an organ, tissue or tumour.
IRON OXIDE NANOPARTICLES
Targeting Agents
Polymer Shells
PEG
Therapeutic Agents
Iron Oxide Core
Currently, there is not a single clinical trial in progress concerning the use of
functionalised IONPs in humans.
13. 13
REGULATORY AND COMMERCIAL FACTORS
Several nanoparticle-based drugs are being clinically used, including liposomal
doxorubicin and albumin conjugate paclitaxel. The carrier-mediated paclitaxel
has exhibited significant efficacy in taxane-resistant cancers, an approach
highly relevant in prostate cancer where taxanes are the treatment of choice.
In addition, studies are focusing on other modifications, including transferrin
receptor and folate receptor targeted drug delivery molecules. These innovative
therapeutic approaches would enable high-concentration targeted drug
delivery to cancer cells with reduced injury of normal cells.
16. 16
OUTLOOKOUTLOOK
Nanoparticles are currently in an early stage of development. They have the
potential and ability to selectively target cancer cells without significantly
damaging healthy tissues. Effectively designed nanoparticles have the ability
to accumulate in tumours, either by passive or active targeting, and enhance
the cytotoxic effects of anti-tumour agents. Several nano formulations of
liposomal and PEG-conjugated liposomal, polymeric micelles anticancer
drugs have been approved, with some already approved for clinical use and
others undergoing phase II and III clinical trials. Moreover, some early phase
clinical trials on AuNPs are in progress.
Cancerous tumours can be eradicated by not only targeting a single site but
also simultaneously using a multiple-target approach. In addition, we may
not have to rely solely on ligand/antibody-modified nanoparticles as a single
tumour-specific marker over-expressed on cancer cells for specific tumour-
targeted delivery. Several studies are underway on ligand-modified AuNPs;
the AuNP-targeting approach can also be used in the future for cancer drug
delivery. Stimulus-based drug delivery is another innovative strategy of
tumour site-specific release of a drug; it is a form of pH-based hyperthermic
therapy. This strategy would require more clinical and commercial research.
Nanoparticles offer the opportunity to reformulate drugs that have been
discontinued due to poor bioavailability, lack of selectivity to desired target
or extreme toxicity. Drug-loaded nanoparticles evade the efflux mechanism
and maintain high concentration within tumour cells, thereby avoiding the
development of resistance. Nanoparticle-based combination therapy for
cancer treatment should focus on the therapeutic chemical and siRNA
combination, co-delivery of chemical and siRNA therapeutics within a single
nanoparticle, and use of multiple nanoparticles for chemical and siRNA
therapeutics.
We expect precisely engineered nanoparticles to emerge as the
next-generation platform for site-specific cancer therapy and several other
biomedical applications. Of the various nanoparticle cancer drug delivery
systems, liposomes, polymer nanoparticles and AuNPs would drive
cancer drug delivery. Thus, the development of nanoparticle drug delivery
strategies that deliver multiple drugs using both active and passive targeting
approaches to multiple cancer cell sites is expected to be
extremely beneficial.