Synthesis and Evaluation of Gemcitabine‐Loaded CdSe/ZnS Quantum Dot‐Based Drug Delivery System for Its Biological Activity

Quantum dots (QDs) have emerged as promising candidates for next‐generation drug delivery systems (DDSs) in oncology, addressing critical limitations of conventional chemotherapeutics, including poor aqueous solubility, non‐specific biodistribution, and rapid clearance. In this study, the clinically approved antitumor agent gemcitabine (GEM) was covalently conjugated to CdSe/ZnS@PEI‐SS‐COOH via esterification chemistry, yielding a functionalized DDS denoted as CdSe/ZnS@PEI‐SS‐COOH‐GEM. This system exhibited superior antiproliferative activity against multiple tumor cells while exhibiting minimal cytotoxicity toward normal cells, thereby demonstrating robust selectivity in cellular targeting. Mechanistic investigations revealed that the DDS exerts antitumor effects through dual induction of autophagy and apoptosis. Fluorescence microscopy and flow cytometry analyses demonstrated significant accumulation of the QDs in tumor cells, accompanied by a marked reduction in mitochondrial membrane potential (MMP), indicative of mitochondrial dysfunction. Western blot assays provided more in‐depth insights into the molecular mechanism underlying the antitumor effect of the DDS. Specifically, the DDS exerted its antitumor activity by upregulating autophagy‐related LC‐3‐II and apoptosis‐related proteins Bak and cleaved PARP‐1, while simultaneously downregulating the expression of antiapoptotic factors PARP‐1 and procaspase‐3. Therefore, this study demonstrates the potential of DDS as multifunctional therapeutic platforms for cancer treatment, providing further exploration and application of DDS in clinical settings.