Surface Engineered Protein Nanoparticles With Hyaluronic Acid Based Multilayers For Targeted Delivery Of Anticancer Agents

Abstract

Layer-by-layer (LbL) technique was employed to modify the surface of doxorubicin (Dox)-loaded bovine serum albumin (BSA) nanoparticles using hyaluronic acid (HA) to enable targeted delivery to overexpressed CD44 receptors in metastatic breast cancer cells. LbL technique offers a versatile approach to modify the surface of colloidal nanoparticles without any covalent modification. Dox-loaded BSA (Dox Ab) nanoparticles optimized for their size, zeta potential, and drug encapsulation efficiency were prepared by modified desolvation technique. The cellular uptake and cytotoxicity of the LbL coated Dox Ab nanoparticles were analyzed in CD44 overexpressing breast cancer cell line MDA-MB-231. Nanoparticles with HA as the final layer (Dox Ab HA) showed maximum cellular uptake in MDA-MB-231 cells owing to the CD44 receptor-mediated endocytosis and hence, exhibited more cytotoxicity as compared to free Dox. Further, luciferase-transfected MDA-MB-231 cells were used to induce tumor in BALB/c female nude mice to enable whole body tumor imaging. The mice were imaged before and after Dox treatment to visualize the tumor growth. The in vivo biodistribution of Dox Ab HA nanoparticles in nude mice showed maximum accumulation in tumor, and importantly, better tumor reduction in comparison with free Dox, thus paving the way for improved drug delivery into tumors.

Hyaluronic Acid Decorated Naringenin Nanoparticles: Appraisal of Chemopreventive and Curative Potential for Lung Cancer

“…The use of HA for targeting tumors has been reported in diverse literature as it possesses number of qualities, viz. biocompatibility and biodegradability owing to its negative charge which can interact better to tumor receptor-like CD44 [ 13 ]. Cancer cells showed a higher expression of CD44 level when compared with normal cells and was recognized as a potential therapeutic target in cancer therapy [ 14 ].…”

Hyaluronic Acid-Modified Polymeric Gatekeepers on Biodegradable Mesoporous Silica Nanoparticles for Targeted Cancer Therapy

“…HA is a key component of the extracellular matrix (ECM) supporting tumor growth for a wide range of human tumors with overexpression of CD44. In addition, HA is well-known for its excellent biocompatibility, biodegradability, low-toxicity, and low-immunogenicity and is currently used in the cosmetic and medical fields . CD44, a major HA receptor, is a multifunctional and multistructural cell surface glycoprotein, capable of detecting changes in ECM components .…”

Recent Developments in Layer-by-Layer Technique for Drug Delivery Applications

“…A few biopolyelectrolytes are listed here dextran sulfate, carboxymethyl cellulose, hyaluronic acid, chitosan, poly- l -lysine, protamine, gelatin A, and so on . Our group has utilized natural biopolymers for designing novel LbL multilayer capsules for specific applications in targeted drug delivery, , gene delivery, , antimicrobial drug delivery, controlled drug delivery using pH-responsive drug release, intracellular-enzyme-responsive drug release, ,,− magnetic-force-controlled drug release, or microshock-wave-triggered drug release . Some of the results are discussed here.…”

“…Further, we proposed a novel route to deliver the drug using LbL multilayer capsules in addition to the preloading and postloading methods, i.e., directly coating the multilayer onto the drug-loaded polymeric nanoparticles, liposomes, and so on without obtaining hollow capsules. , Herein, we employed a hyaluronic acid (HA) and poly­( l -lysine hydrobromide) (PLL) multilayer coating to protect Dox-encapsulated bovine serum albumin (BSA) nanoparticles (Dox Ab HA) from premature leakage and also target the particles to metastatic breast cancer cells as shown in Figure C . The specific targeting of breast cancer cells was achieved by keeping HA as a top layer to interact with overexpressed CD44 receptors on the cancer cells.…”