Investigating the Encapsulation and Selectivity of Functionalized Mesoporous Silica Nanoparticles : CA IX vs Folate receptors

Sahoo, Rakesh (2019) Investigating the Encapsulation and Selectivity of Functionalized Mesoporous Silica Nanoparticles : CA IX vs Folate receptors. Masters thesis, Indian Institute of Science Education and Research Kolkata.

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Abstract

A drug efficient to its cause may also result in severe side effects. Delivering the drugs to the target cells would reduce the side effects. A cell may be targeted by the receptors it expresses on its surface. Cancer cells are known to express receptors that help carry a faster metabolism. Folate, transferrin, glucose and various amino acid receptors are known to be more expressed on cancer cells. Apart from that, the constricted space resulting from uncontrolled growth of cells leads to hypoxia and reduction in pH of the interstitial space between the cancers cells. This leads to more expression of carbonic anhydrase-IX (CA-IX) and carbonic anhydrase-XII (CA-XII) on the membrane of cancer cells. Currently many highly active anticancer agents are coming up but they have the problem of being toxic to healthy cells. It is known that folate is a good target and there many reports of the folate fuctionalized nanoparticle. The exploitation of the overexpression of CA-IX on cancer cells is relatively less. Although there are excellent molecules that can bind to CA-IX and have the potential to be fuctionalized on mesoporus silica nanoparticles (MSNs) which are known to be excellent for drug delivery. MSN are considered to be relatively better tolerant delivery vehicle and facilitates fictionalization along with gating for controlled release of drugs. The large surface area, tunable porosity, structural diversity, variable size, easily customizable surface and its high compatibility for fictionalization have been extensively adopted. In this thesis work, we have performed the syntheses and surface modifications for MSNs for targeting Carbonic Anhydrase- IX (CA-IX) and folate receptors to compare which one is a better target for gaining selectivity. The MSNs are 30-50 nm in size as per transmission electron microscopy and their hydrodynamic radii very between 150 – 250 nm. We have characterized the surface functionalization of the nanoparticles by NMR. We have then probed the drug loading capacity of the surface functionalized nanoparticles using Rhodamine 6G dye. We found that folate functionalized MSNs show higher loading capacity then the CA – IX inhibitor functionalized MSNs. Thus the synthetic challenges faced and the low drug loading capacity suggests that it is necessary to have the pores gated through additional surface functionalization upon loading the drugs.

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