Integrated and hyaluronic acid-coated mesoporous silica nanoparticles conjugated with cisplatin and chlorin e6 for combined chemo and photodynamic cancer therapy

• Multifunctional nanomedicine with ultra-stable integrated nanostructure is prepared. • This nanosystem is biocompatible and has the ability to target tumor cells. • This nanosystem has the ability to improve tumor therapy efficiency through combined chemo and photodynamic therapy . To enhance antitumor efficacy and overcome multidrug resistance, the targeted delivery of photosensitizers and chemotherapeutic agents holds great promise for improving anticancer effects. In this study, we aim to enhance the targetability and solubility of chlorin e6 (Ce6), an FDA-approved second-generation photosensitizer, by conjugating it to hyaluronic acid (HA) via glutathione-responsive cystamine linkages (HA-SS-Ce6). These conjugates are then utilized to coat cisplatin (CP)-loaded functionalized mesoporous silica nanoparticles (MSNs), resulting in a simple and efficient chemo-photodynamic combination nanoplatform targeting cancer cells (MSNs@HG-Ce6/CP). Cellular uptake tests demonstrate effective cancer cell targeting of the nanoparticles by MSNs@HG-Ce6 in MDA-MB-231 cells, with intracellular redox-responsive release of Ce6. The released Ce6 generates cytotoxic reactive species, induces oxidative stress, and subsequently triggers apoptosis upon near-infrared light irradiation. Importantly, the combinatorial MSNs@HG-Ce6/CP system synergizes the therapeutic effects of both the photosensitizers and the chemotherapeutic agents. In vivo chemo-photodynamic therapy tests of MSNs@HG-Ce6/CP show prolonged blood circulation upon systemic administration into MDA-MB-231 tumor-bearing mice, leading to increased accumulation of Ce6 and CP in tumor tissues, as observed through real-time in vivo imaging. Consequently, near-infrared light irradiation of mice treated with MSNs@HG-Ce6/CP effectively suppresses tumor growth. These findings suggest that the targeted chemo-photodynamic combination therapeutic platform holds promise for synergistic cancer therapy.