Biopolymer Silica Hybrids as Superior Nanocarriers for Anticancer Drug Delivery

Abstract Liposomal carriers are widely used for anticancer drug delivery due to their biocompatible nature in the biological milieu. Liposome-based drugs often face premature leakage, uncontrolled release, and insufficient control over long-term drug availability. Here, we present poly(lactic-co-glycolic acid) (PLGA)-coated mesoporous silica nanocarriers (PLGA–mSiO2, polysilomes) as an efficient and stable alternative to PEGylated liposomes. Such hybrid transporters are capable of efficiently encapsulating both hydrophilic [doxorubicin (DOX)] and hydrophobic [tamoxifen (TAM)] drugs. Investigation on drug loading, release kinetics, cellular uptake, and therapeutic response confirms the superior drug encapsulation and delivery of polysilomes efficiently. In liposomes, TAM was localized within the lipid bilayer, whereas DOX was actively loaded into the aqueous core through a transmembrane pH gradient. While this architecture enabled coloading, liposomes showed rapid drug release and pronounced cytotoxicity. In contrast, the core–shell structure of PLGA–mSiO2 polysilome carriers retained hydrophilic DOX within the mesoporous silica core and hydrophobic TAM within the PLGA shell. This compartmentalization ensures higher encapsulation efficiencies of both DOX (77.3%) and TAM (60.5%), with loading capacities of 59.3 and 50.4%, respectively. The PLGA–silica interface is a degradable diffusion barrier, enabling pH-responsive sustained release under acidic conditions. Moreover, PLGA–mSiO2 showed enhanced cellular uptake in MDA-MB-231 breast cancer cells and prolonged (up to 144 h) suppression of cell viability. These results present PLGA-coated mesoporous silica nanocarriers as a promising alternative to liposomal delivery by converting rapid drug release into sustained therapeutic activity.