摘要
The delivery of nanoparticles encounters a series of biological barriers from systemic clearance, tumor accumulation, cellular uptake and intracellular drug release. In this study we propose enzyme-powered nanomotors launched from intratumorally injected local depots to overcome these delivery barriers. Hydroxyapatite-embedded mesoporous silica nanoparticles ( [email protected] ) are prepared by formation of silica layers on CaCO 3 nanoparticles, transformation of CaCO 3 into Hap cores, and camptothecin (CPT) loading. Janus nanoparticles (JPs) are obtained by the selective deposition of gold layer on one side of [email protected] Janus nanomotors (JNMs) are constructed by separately grafting hyaluronic acid (HA) and urease on the opposite sides of JPs as the targeting moiety and power source, respectively. JNMs indicate self-propelled motion under the physiological concentration of urea (5 mM), and the motion is less disturbed in the dense tumor matrix. Despite no influence on the endocytosis mechanism, the self-propelled motion and HA-mediated targeting enhance the cellular uptake and cytotoxicity of JNMs. JNMs rapidly release the encapsulated CPT in the acidic endo/lysosomes of tumor cells (pH 5.0) while maintaining their integrity (CTP release <10%) in physiological conditions (pH 7.4) and tumor matrix (pH 6.5). In addition, JNMs are loaded into electrospun fiber fragments ( [email protected] ) for intratumoral administration to achieve a high retention and gradual release of JNMs in response to the slightly acidic tumor matrix (pH 6.5). The self-propelled motion promotes the deep penetration and even distribution of JNMs in tumors, dramatically enhancing the antitumor efficacy. Therefore, the launching of nanomotors from intratumoral depots is a feasible strategy to boost the antitumor efficacy via promoting the local accumulation, deep tumor penetration, tumor cell capture and intracellular release of chemotherapeutic drugs.
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