MULTIFUNCTIONAL NANOPLATFORMS FOR SUBCELLULAR DELIVERY OF DRUGS IN CANCER THERAPY
Madiha Ashraf , Laiba Sattar, Bushra Siddique
The University of Lahore 1-KM Defence Road Lahore
MECHANISM
properties of pa rti cles and the types of cells , there
Chemotherapy and radiation therapy are
a re two major internaliza tion mechanisms :
traditional cancer treat ments which are phagocytosis and pinocytosis . Phagocytosis is the
constrained by side effects associated with drug. It
process of cell ea ting, usuall y occurs in
is due to lack of targeted delivery techniques for
internalization of la rge pa rti cles; and pinocytosis is
transporting anticancer med icines to the a l so ca lled as cell drinking,
neoplastic tissue. Targeted delivery of anticancer
agents is very vital to reduce these side effects .
Recent developments in nanoparticle (NP)-based
drug delivery systems (NDDSs) have
demonstrated that they can carry drugs to
pathological tissues via cell-memb rane targeting
and release these drugs in the cytoplasm After
successful delivery into the targeted cell, a drug
should get access to a particular organelle
(endo/lysosome mitochondria, Golgi apparatus,
nucleus, etc.) to be effective
• PHAGOCYTOS IS
P hagocytosis mostly occurs in professional phagocytes,
including polymorphonuclear leucocytes and mononuclear cells
such as macrophage and monocytes
• PINOCYTOS IS
P inocytosis occurs in all cell types [18]. For cancer associated
delivery, tumor cells belong to non-phagocytic cells, can take in
particles up to 500 nm [19], there fore, pinocytosis is more
relevant to the uptake of NP s by tumor cells.
Clathrin-mediated endocytosis (CM E).
This is the main pathway for cellular entry. CME happens with
the assistance of clathrin, a cytoplasmic protein. CME allows for
the cellular internalization by decorating NPs with particular
ligands, which are capable of recognizing the specific receptors
over expressed on the cell membranes [
• PAS S IVE TARGETING
The blood vessels in tumor tissues are fr equently
perme able, so NP s can passively target tumors via the
enhanced permeation and retention (EP R) effect [29]. The
EP R effect has beco me an e ffective means for delivery of
anticancer drugs to tumors by using polymer conjugates or
liposomes.
• S IZE
P article size also influences the process of crossing the cell
me mb rane. The results showed that the 100 nm and 200 n m
polystyrene
• S HAPE
Numerous shapes of NP s are able to be constructed due to
the rapid development in the technologies. Spheres, rods,
cylinders, sphero-cylinders have been researched to date .
Non-spherical NP s are widely used, especially in the
cellular uptake.
• S URFACE CHARGE
It is well-known that positively charged NP s tend to have a
higher rate of cell uptake in comparison with the neutral
and negatively charged NP s . Slight surface charge
differences remarkably influenced the internalization .
• ACTIVE TARGETING
Active targeting has been efficiently increase the cancer cell
entry of NP s and improves their therapeutic effects. NP s
with actively targeted ligands recognize and bind to
specific rec eptors, which are e xpressed a lot on cancer cells
and minimal on normal cells.
CONCLUS ION
The goal of nanoparticle-based drug delivery is to
selectively deliver drugs to a target, which decreases side
effects and increases therapeutic efficiency. It can accelerate
the development of personalized and precision medicine.
The therapeutic outcome can be influenced by controlling
the uptake route of NPs. In this review, several targeting
strategies have been discussed, such as optimizing the
physico-chemical properties of NPs, by using cell
penetrating peptides. A detailed understanding of the
intracellular trafficking of subcellular targeted
nanomedicines, as well as their time-dependent fate and
drug release profile inside the organelles still remains
lacking. Although the task is challenging, sequential
multistage
❑ Wilhelm S, Tavares AJ, Dai Q, Ohta S, Audet J, Dvorak HF, et al. Analysis
of nanoparticle delivery to tumours. Nat Rev Mater 2016;1:16014.
❑ Shi J, Kantoff PW, Wooster R, Farokhzad OC. Cancer nanomedicine:
progress, challenges and opportunities. Nat Rev Cancer 2017;17:20.
❑ Torchilin VP. Recent approaches to intracellular delivery of drugs and
DNA and organelle targeting. Annu Rev Biomed Eng 2006;8:343–75.
We would like to gratefully acknowledge
the different grand rec eived in order to
accomplish the research work in progress in
this field .We are thankful and greatful to
our head of department ,faculty staff and
teachers who fully help and co operate with
us during this research work