ABSTRACT
The limitations of self-assembled polymeric nanoparticles for cancer therapy, including instability in the bloodstream, non-specific targeting of cancer cells, and unregulated intracellular drug delivery, were effectively addressed by the development of core-shell SNX@PLL-FPBA/mHA NPs. The core was SNX@PLL-FPBA NPs prepared from polylysine conjugated 3-fluoro-4-carboxyphenylboronic acid (PLL-FPBA) self-assembly and SNX encapsulation, while the shell was methacrylate-modified hyaluronic acid (mHA) adhering to the core by electrostatic interactions and subsequently stabilized by photo-crosslinking, without the use of any organic solvent. SNX@PLL-FPBA/mHA NPs exhibited good stability in varying ionic strengths (0-0.30 M NaCl), pH levels (6.8 and 7.4), and plasma environments mimicking the blood, ensuring their efficacy in systemic circulation. The drug delivery from the nanoparticles was highly sensitive to ATP/Hyals stimuli (82 % within 48 h), closely mimicking the intracellular environment of breast cancer cells. The nanoparticles demonstrated good hemocompatibility and non-toxicity towards human skin fibroblasts. Efficient internalization of SNX@PLL-FPBA/mHA NPs by MCF-7 and MDA-MB-231 breast cancer cells was observed by CLSM and flow cytometry. The intracellular ATP/Hyals stimuli triggered the rapid drug delivery and induced cellular apoptosis. Thus, SNX@PLL-FPBA/mHA NPs were a promising drug nanocarrier for breast cancer therapy, offering improved stability, targeted delivery, and controlled drug release to enhance treatment outcomes.
Subject(s)
Adenosine Triphosphate , Apoptosis , Breast Neoplasms , Drug Carriers , Hyaluronic Acid , Nanoparticles , Polylysine , Humans , Adenosine Triphosphate/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Boronic Acids/chemistry , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Drug Carriers/chemistry , Drug Delivery Systems , Drug Liberation , Hyaluronic Acid/chemistry , Hyaluronic Acid/pharmacology , MCF-7 Cells , Nanoparticles/chemistry , Polylysine/chemistryABSTRACT
Tear protein deposition and bacterial adhesion are the main drawbacks of the hydrogel contact lens. In this study, we developed a novel superhydrophilic poly(2-hydroxyethyl methacrylate) (NSCC-pHEMA) hydrogel with nanosilica covalent coating by the combination of colloidal silica immersion and dehydration treatment. The infrared spectroscopy and energy dispersive X-ray spectroscopy analyses confirmed the successful formation of Si-O covalent bonding between nanosilica and pHEMA hydrogel. This coating was highly stable against powerful sonication or long-term shaking immersion treatment. Among various NSCC-pHEMA hydrogels with different colloidal silica concentrations, the 7%NSCC-pHEMA hydrogel generated a superhydrophilic micro wrinkle surface with a root-mean-square roughness of 43.10 nm, which dramatically reduced the deposition of lysozyme and bovine serum albumin by 65% and 57%, respectively, and decreased the adhesion of S. aureus and E. coli by 59% and 66%, respectively, in comparison to the pHEMA hydrogel. However, the nanosilica coating had little effect on the mechanical properties, light transmittance, oxygen permeability, and equilibrium water content of the pHEMA hydrogel. NSCC-pHEMA hydrogels were nontoxic to both mouse fibroblasts (L929) and human immortalized keratinocytes (HaCaT). Thus, the superhydrophilic NSCC-pHEMA hydrogel is a potential contact lens material for resisting tear protein deposition and bacterial adhesion.