Search

Because of the nontargeting release of anticancer drugs, conventional chemotherapy results in serious side effects and poor therapeutic outcomes. In addition, hypoxia situation in the tumor microenvironment also promotes the growth and metastasis of tumors. Multifunctional nanocarriers with stimuli-activation and hypoxia-relieving properties can help overcome some of these limitations. In this study, we have constructed a nanocarrier which is named PBMn–DOX@RBC. A Prussian blue/manganese dioxide (PBMn) nanoparticle is used as an oxygen precursor or catalyzer for H2O2activation, and a red blood cell (RBC) membrane is used to increase the loading capacity of doxorubicin (DOX) and prolong the circulation time in vivo. H2O2is overproduced in tumor tissues and tumor cells. It can be used as a stimulus to activate drug release. In the presence of H2O2, the hypoxia inside the tumors is relieved by the administration of PBMn–DOX@RBC. The generated oxygen disrupts the RBC coated on the surface of PBMn, which accelerates the release of DOX. RBCs also prolong the circulation time of the nanometer system in vivo. By combining the photothermal therapy (PTT) and chemotherapy, the tumor growth inhibition mediated by PBMn–DOX@RBC is further enhanced. PBMn–DOX@RBC fulfills the demands to relieve tumor hypoxia and enhance cancer chemotherapy/PTT.

Nanoparticle-based systems explore not only the delivery efficacy of drugs or contrast agents, but also additional capabilities like reducing the systemic toxicity, especially during cancer chemotherapy. Since some of the noble metal nanoparticles exhibit the catalysis properties which can scavenge the reactive oxygen species (ROS), they can be used as a promising drug delivery platform for reducing the oxidative stress damage in normal tissues caused by some chemotherapy drugs. Herein, in this study, we construct porous Au@Pt nanoparticles and further explore the properties of porous Au@Pt nanoparticles in relieving the oxidative stress damage as well as in tumor growth inhibition by chemo-photothermal co-therapy. The tunable surface pore structure of Au@Pt nanoparticle provides space for Doxorubicin (DOX) loading. cRGD peptide modification enable the DOX-loaded Au@Pt nanoparticles to improve drug delivery properties. The constructed nanocarrier (DOX/Au@Pt-cRGD) shows controlled drug release behavior. Meanwhile, the absorbance peak of the Au@Pt structure in the near-infrared (NIR) portion provides the capacity for in vivophotoacoustic imaging and the high photoconversion efficiency, which make Au@Pt nanoparticle a suitable carrier for photothermal therapy (PTT). Combined with chemotherapy, the nanosystem DOX/Au@Pt-cRGD shows enhanced anticancer therapeutic effects. More importantly, ROS-scavenging activity of Au@Pt alleviates the DOX-induced oxidative stress damage, especially the cardiomyopathy during chemotherapy. Herein, this nanosystem DOX/Au@Pt-cRGD could be explored as reactive oxygen scavenger and drug delivery system for side effects relieving chemo-photothermal combinational therapy.

The natural flavonoid fisetin (3,3′,4′,7-tetrahydroxyflavone) was discovered to possess antitumor activity, revealing its potential value in future chemotherapy. However, its poor water solubility makes it difficult for intravenous administration. In this study, the monomethyl poly(ethylene glycol)–poly(ε-caprolactone) (MPEG–PCL) copolymer was applied to prepare nanoassemblies of fisetin by a self-assembly procedure. The prepared fisetin micelles gained a mean particle size of 22 ± 3 nm, polydisperse index of 0.163 ± 0.032, drug loading of 9.88 ± 0.14%, and encapsulation efficiency of 98.53 ± 0.02%. Compared with free fisetin, fisetin micelles demonstrated a sustained and prolonged in vitrorelease behavior, as well as enhanced cytotoxicity, cellular uptake, and fisetin-induced apoptosis in CT26 cells. As for in vivostudies, fisetin micelles were more competent for suppressing tumor growth and prolonging survival time than free fisetin in the subcutaneous CT26 tumor model. Furthermore, histological analysis, terminal deoxynucleotidyl transferase-mediated nick-end labeling assay, immunohistochemical detection of Ki-67, and microvessel density detection were conducted, demonstrating that fisetin micelles gained increased tumor apoptosis induction, proliferation suppression, and antiangiogenesis activities. In conclusion, we have successfully produced a MPEG–PCL-based nanocarrier encapsulating fisetin with enhanced antitumor activity.