RESUMEN
Considering that photodynamic therapy (PDT)-induced oxygen consumption and microvascular damage could exacerbate hypoxia to drive more glycolysis and angiogenesis, a novel approach to potentiate PDT and overcome the resistances of hypoxia is avidly needed. Herein, morpholine-modified PEGylated bilirubin was proposed to co-deliver chlorin e6, a photosensitizer, and diclofenac (Dc). In acidic milieu, the presence of morpholine could enable the nanocarriers to selectively accumulate in tumor cells, while PDT-generated reactive oxidative species (ROS) resulted in the collapse of bilirubin nanoparticles and rapid release of Dc. Combining with Dc showed a higher rate of apoptosis over PDT alone and simultaneously triggered a domino effect, including blocking the activity and expression of lactate dehydrogenase A (LDHA), interfering with lactate secretion, suppressing the activation of various angiogenic factors and thus obviating hypoxia-induced resistance-glycolysis and angiogenesis. In addition, inhibition of hypoxia-inducible factor-1α (HIF-1α) by Dc alleviated hypoxia-induced resistance. This study offered a sequentially responsive platform to achieve sufficient tumor enrichment, on-demand drug release and superior anti-tumor outcomes in vitro and in vivo.
RESUMEN
Nucleic acid drugs are highly applicable for cancer immunotherapy with promising therapeutic effects, while targeting delivery of these drugs to disease lesions remains challenging. Cationic polymeric nanoparticles have paved the way for efficient delivery of nucleic acid drugs, and achieved stimuli-responsive disassembly in tumor microenvironment (TME). However, TME is highly heterogeneous between individuals, and most nanocarriers lack active-control over the release of loaded nucleic acid drugs, which will definitely reduce the therapeutic efficacy. Herein, we have developed a light-controllable charge-reversal nanoparticle (LCCN) with controlled release of polyinosinic-polycytidylic acid [Poly(I:C)] to treat triple negative breast cancer (TNBC) by enhanced photodynamic immunotherapy. The nanoparticles keep suitably positive charge for stable loading of Poly(I:C), while rapidly reverse to negative charge after near-infrared light irradiation to release Poly(I:C). LCCN-Poly(I:C) nanoparticles trigger effective phototoxicity and immunogenic cell death on 4T1 tumor cells, elevate antitumor immune responses and inhibit the growth of primary and abscopal 4T1 tumors in mice. The approach provides a promising strategy for controlled release of various nucleic acid-based immune modulators, which may enhance the efficacy of photodynamic immunotherapy against TNBC.
RESUMEN
Traditional chemotherapy exhibits a certain therapeutic effect toward malignant cancer, but easily induce tumor multidrug resistance (MDR), thereby resulting in the progress of tumor recurrence or metastasis. In this work, we deigned ternary hybrid nanodrugs (PEI/DOX@CXB-NPs) to simultaneously combat against tumor MDR and metastasis.
RESUMEN
Stimuli-responsive nano drug delivery systems based on specific structures and physicochemical properties of tumor have been drawing wide attention from researchers, one of which is charge-reversal nano drug delivery system(CRN-DDS). CRN-DDS can effectively combine the merits of positive and negative charges in the drug delivery process in vivo, and it also has the good property of tumor-targeting. Although studies of CRN-DDS application in cancer therapy have already been reported, there is very little relevant Chinese literature, especially review articles. To fill in the blank, the foreign literatures about CRN-DDS were looked up in the last six years, classified CRN-DDSs by their different approaches of surface charge reversal, and summarized the studies on their applications in the cancer therapy. Last but not least, the prospect of CRN-DDS's development and application was preliminarily looked into in this article.
RESUMEN
pH-responsive nanoparticles (NPs) are currently under intense development as carriers of drug delivery systems for cancer therapy. Of these NPs, those that are designed to target the slightly acidic extracellular pH environment (pHe~6.8) of solid tu-mors offer a new paradigm of tumor-targeted drug delivery. Compared with conventional, specific, surface-targeting approaches, the pHe-targeting strategy is considered to be more general because of the common occurrence of an acidic microenvironment in solid tu-mors. This review mainly focuses on the design and applications of pHe-activated NPs, particularly on pHe-activated surface-charge re-versal NPs, for drug and siRNA delivery to tumors. The novel development of NPs described in this review has high potential for achieving stronger therapeutic effects in cancer treatment.