The document discusses various types of nanoparticles used in nanomedicine, including their properties and applications. It describes how nanoparticles can accumulate in tumors via the enhanced permeability and retention effect. Different classes of nanoparticles are described, such as liposomes, polymers, inorganic nanoparticles, and extracellular vesicles like exosomes. The advantages of these nanoparticles for drug delivery, imaging, and theranostics are summarized. Key factors that influence the behavior of nanoparticles in the body like size, shape, surface properties are also discussed.

1. NANOMEDICINEs
By
Mohie-Aldien Elsayed Sherief
Professor of pharmacology, Faculty of Medicine,Benha University

2. Medical Nanomachines and Nanorobots

3. Theranostics publishes innovative research articles reflecting the fields of in vitro diagnostics and prognostics

4. The enhanced permeability and retention effect (EPR effect) describes a universal
pathophysiological phenomenon and mechanism in which macromolecular compounds such as albumin
and other polymer-conjugated drugs beyond certain sizes (above 40 kDa) can progressively accumulate
in the tumor vascularized area and thus achieve targeting delivery and retention of anticancer
compounds into solid tumor tissue.
Targeting therapy via the EPR effect in clinical practice is not always successful since the strength of the
EPR effect varies depending on the type and location of tumors, status of blood perfusion in tumors,
and the physical-chemical properties of macromolecular anticancer agents
•Stabilization processes to prevent the nanoparticles from agglomeration are.very important.
•Making a same size distribution of nanoparticles is an important.factor, which can be controlled by
diffusion-limited growth processes or byconfining the growth space

6. Nature Reviews Drug Discovery volume 20, pages101–124 (2021)
(bilayer structures from lipids
Classes
of NPs.

8. Different
types of
nanoparticles
(NPs) for
cancer
therapy.

9. PEGylated liposome: polyethylene glycol,(PEG) in pharmacy called macrogo.is grafted onto the surface of NPs by
(a) physical adsorption, (b) covalent coupling, and (c) copolymer self-assembly grafting of PEG to the surface of NPs
•PEGylated liposome high molecular size, high solubility, and shielding against the
recognition by opsonin.
•Conventional liposome: small molecular size, low solubility, and recognition by opsonin.

10. Bovine serum albumin
Glutathione
Methoxypoly(ethyleneglycol)
thiol
EPR: Enhanced permeability and retention; RES: Reticuloendothelial system
.
Poly(lactide-co-glycolide)
acid; PLG-g-mPEG: Poly(l-
glutamic acid)-g-methoxy
poly(ethylene glycol

11. Nanomedicine (Lond.) (2018) 13(12), 1495–1512

12. Exosomes,(extracellular vesicles) as natural nano-scale particles, have various advantages in comparison with other
engineered nanoparticles Exosomes are secreted by MSCs and have the same therapeutic potential as their parent cells.
MSCs and their exosomes combined with biomaterials can also be more effective in promoting the regeneration of tissues

13. A large number of studies show that EVs released by stem cells have repair functions similar to
stem cells

14. The main advantages can be summarized as follows.
•First, exosomes are the mediators of stem cell paracrine action. They participate in the
transmission of information between cells and are considered to be the main mechanism of
disease treatment.
•Second, exosomes can be combined with existing, newly developed compositions or methods
and designed as carrier particles containing specific ingredients. In addition, they can be
engineered to target specific cells or tissues.
•Third, exosomes have autonomous targeting capabilities and can home to the lesion tissue,
which is conducive to constructing them into drug carriers.
All these characteristics facilitate exosomes to be the ideal natural material for the development
of nanomedicine (Mathieu et al., 2019). Compared with cell therapy, it is safer and has no
potential tumorigenicity of stem cells. It is the best alternative to cell-free therapy at present.
•achieve similar effects to synthetic nanoscale carriers (such as liposomes, nanoparticles),
but also have cell-based biological structures and functions.
• exosomes can provide natural biocompatibility; higher chemical stability; longer
distance intercellular communication; and inherent intercellular communication, fusion,
and delivery capabilities.
•exosomes have the ability to selectively fuse cells and target specific tissues as well as to
penetrate tight tissue structures, such as the blood–brain barrier

15. pharmacokinetics and biodistribution of the
nanoparticles

16. In comparison with conventional DDSs, drug administration using nanoparticles
(NPs) has several advantages, :

17. Pharmacokinetic functions of organs on nanoparticles (NPs). (A) Pharmacokinetic scheme. (B)
Nanoparticle(metabolic pathways in vivo).

18. • .

19. Quantum dots, hollow spheres
dimensions <100 nm
• Treat prostate cancer with fewer side effects
thanchemotherapy
• particularly efficient inevading the reticuloendothelial
system.
• AuNPs for cancer phototherapy
• Photodynamic therapy (PDT)
• Sonodynamic therapy (SDT) is utilized in
activation of the cytotoxic effect of chemicalcompounds
(sonosensitizers) and

21. The pharmacokinetics, pharmacodynamics and toxicity of theranostic NPs. Shown are
absorption, biodistribution, elimination and pharmacologic and toxic effects of NPs following
different routes of administration. The fate of the theranostic NPs depends on physicochemical
properties of NPs and the route of administration as well as altered body functions (e.g.,
nutrition status and disease conditions)
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22. Nature Reviews Drug Discovery volume 20, pages101–124 (2021)
Factors such as size, shape, charge and surface coating determine what happens to nanoparticles (NPs) in
the circulation, including clearance, and how the NPs interact with local barriers such as the tumour
microenvironment or mucus layers.
spherical and larger NPs marginate more easily
during circulation, whereas rod-shaped NPs
extravasate more readily;
uncoated or positively charged NPs are
cleared more quickly by macrophages
in general, rod-shaped, neutral and targeted
NPs penetrate tumours more readily positively charged, smaller and coated NPs
more easily traverse mucosal barriers

23. Nature Reviews Drug Discovery volume 20, pages101–124 (2021)
Common uptake pathways that ultimately determine NP fate within a
cell.

24. Active and passive uptake of nanoparticles. NPs, Nanoparticles; EPR, Enhanced permeability retention

25. Passive
targeting of
NPs
→(EPR)→↑
vascular
permeability
and weakened
lymphatic
drainage of
cancer cells
Active targeting
is achieved by
the interaction
between ligands

26. Administration of pH sensitive peptide drug via oral delivery. a The peptide drug administered
orally degraded particularly in stomach due to proteolytic enzymes which result in poor
availability of drugs. b The nanoparticles shields drugs and prevent from enzymatic degradation.
Hence attains the efficient distribution of drugs

28. The usage of composite nanomaterials in biomedical engineering applications
Biotech & Bioengineering, Volume: 118, Issue: 8, Pages: 2906-2922, First published: 29 May 2021, DOI: (10.1002/bit.27843)

29. Illustration of the type, synthesis characterization and functionalization NPs and their
application for tissue engineering.

30. Nanotechnologies and Nanomaterials in 3D (Bio)printing toward Bone Regeneration
Advanced NanoBiomed Research, Volume: 1, Issue: 11, First published: 11 August 2021, DOI: (10.1002/anbr.202100035)

31. Illustration of hydroxyapatite-based scaffold-induced regeneration of bone.
DOI: 10.1039/D1RA01849C (Review Article) RSC Adv., 2021, 11, 19041-19058

32. Schematic representation of bone regeneration using nanotechnology.
September 2014International Journal of Nanomedicine 9(Issue 1):4153-416
Notes: Improved bone healing using (A) nanofibrous scaffold and (B) culturing MSCs on nano matrices.
Abbreviation: MSCs, mesenchymal stem cells.

34. Various nanotechnology-based methods for skin regeneration.
September 2014International Journal of Nanomedicine 9(Issue 1):4153-416
Nanotechnology application in wound healinghas anano fibrous scaffolds. Addition of
Growth factors,Stem cells,Gene therapy and nanomaterials and atargeted delivery of drugs
help the wounds heal faster

37. Surface modification showing improved performance and longevity of dental implants.
September 2014International Journal of Nanomedicine 9(Issue 1):4153-416
Abbreviation: HA, hydroxyapatite.
M a t e r i a l s t o i n d u c e b o n egrowth:Hydroxyapatite nanoparticles are usedto treat bone defects.Nanocrystals have modified
surface with nanopores that adsorb proteins.Calciumsulphate is used to fill small spaces foundin post extraction tooth sockets. It is used in
periodontal bone defects and as an adjunct to thelonger lasting bone graft material.

38. Essential elements in cartilage tissue engineering

40. application of nanotechnology in varied therapies for oncology
where nanoparticles helps in improving the pharmacokinetics of the therapeutic agent
andselective targeting of tumor

41. Summary of NP effects in cancer environments
Nature Nanotechnology volume 16, pages1180–1194 (2021

42. Nanophototherapies for CancerTreatment
Current treatments (chemotherapy,surgery and radiotherapy )all have benefits
and weaknesses,mostly involving some limitation on selectivity or
precision.
• Nanophototherapies attempt to overcome these problems
by combining single-cell treatments with cancer-only
damage selectivity.
• Attaching antibodies to the nanoparticles and injecting
them into the body should result in the accumulation of
those nanoparticles at or near the tumor.
• Depending on the selectivity of the molecule used, this can
lead to a somewhat higher concentration of nanoparticles
in cancer cells.

43. Nanophotothermolysis is a selective thermal killing
of cancer cells targeted by the absorbing nanoparticlesheated by the radiation.
.(1)Gold nanorods are solid cylindersas small as 10 nm in diameter. With differentcombinations of diameter and
length of nanorods,the wavelength of light that the nanorod absorbscan be changed.
(2) Nanospheres have gold coating overa silica core.Changes made in the thickness of thegold coating and in the
diameter of the silica corethe wavelength of the light that the nanosphereabsorb may be altered

44. The potential advantages of nanotechnology for photothermalbased
killing of abnormal cells targeted with absorbingNanoparticles.
•sensitizers heated with radiation include:
-Selective cancer-cell targeting by means of conjugation ofabsorbing
particles with specific antibodies.
•Localized tumor damage without harmful effects on
surrounding healthy tissue.
•No undesired side-effects (e.g., cytotoxicity or cutaneous
photosensitivity).
•Relatively fast treatment involving potentially just one or
several pulses of radiation

45. Nanomaterials 2021, 11, 3346

46. Treatment of obesity with PTT.
(A) Gold nanoparticles are injected into adipose tissue.
(B) Irradiation of epidermis with 800 nm laser increases the temperature of gold nanoparticles
and liquefies small volumes of fat.
(C) Adipose tissue and gold nanoparticles were removed by a liposuction program.

48. Tradename Nanoplatform and active agent Application Approval (date) Company
Adynovate®/Adynovi® PEGylated recombinant anti-hemophilic factor Hemophilia FDA (2015) EMA (2017) Takeda
Aristada® Aripiprazole lauroxil nanocrystals Schizophrenia FDA (2015) Alkermes
Glatopa® (Generic of
Copaxone)
Random copolymer of L-glutamate, L-alanine,
L-lysine, and L-tyrosine
Multiple sclerosis FDA (2015) Novartis
Invega Trinza®/Trevicta® Paliperidone palmitate nanocrystals Schizophrenia FDA (2015) EMA (2016) Janssen
Inveltys® Loteprednol etabonate nanosuspension Post-operative ophthalmic
inflammation
FDA (2018) KALA
pharmaceuticals
Mircera® PEGylated epoetin beta Anemia in chronic renal diseases
for pediatric patients
FDA (2018) EMA (2019) Vifor
mRNA-1273 Lipid nanoparticle of full-length, prefusion
stabilized spike protein mRNA
Prevention of COVID-19 FDA (2020) EMA (2021) Moderna
Onpattro® (Patisiran) Lipid nanoparticle for siRNA targeting TTR
protein
TTR-mediated amyloidosis FDA and EMA (2018) Alnylam
Pharmaceuticals
Onivyde® PEGylated liposomal irinotecan Metastatic pancreatic cancer FDA (2015) EMA (2016) Merrimack
Rebinyn®/Refixia® PEGylated glyco-protein drug Hemophilia FDA and EMA (2017) NovoNordisk
Sublocade® Buprenorphine-loaded PLGA nanoparticles Opioid use disorder FDA (2017) Indivior
Tozinameran® Lipid nanoparticle of full spike mRNA Prevention of COVID-19 FDA and EMA (2020) BioNTech SE and
Pfizer
Vyxeos® Liposomal formulation of cytarabine:
daunorubicin (5:1 M ratio)
Acute myeloid leukemia FDA (2017) EMA (2018) Jazz
Pharmaceuticals
Zilretta® PLGA hydrogel of triamcinolone acetonide Knee osteoarthritis FDA (2017) Flexion Therapeutics
FDA- and EMA-approved nanomedicines
FDA Food and Drugs Administration, EMA European Medicines Agency, TTR transthyretin, PLGA poly(lactic-co-glycolic acid), PEG polyethylene
glycol, COVID-19 coronavirus disease 2019
Drug Delivery and Translational Research (2022) 12:500–525

49. Drug Delivery and Translational Research (2022) 12:500–525

50. Nano-toxicological classification
Most inorganic
.NP(gold)
SilicaNP
LIPID-BAS.
Polymeric NP

54. The global
nanomedicine
market revenue
trends and (b) US
nanomedicine
market size for by-
products

55. THANKS

56. Important points that need to be considered when designing asynthesis process are:
•Synthesis of nanoparticles is possible in all three phases: liquid, solid and
gaseous.
•Stabilization processes to prevent the nanoparticles from agglomeration are
very important.
•Making a same size distribution of nanoparticles is another important
factor, which can be controlled by diffusion-limited growth processes or by
confining the growth space