Background Cancer is one of the devastating diseases in the world. The development of nanocarrier provides a promising perspective for improving cancer therapeutic efficacy. However, the issues with potential toxicity, quantity production, and excessive costs limit their further applications in clinical practice. Results Herein, we proposed a nanocarrier obtained from aloe with stability and leak-proofness. We isolated nanovesicles from the gel and rind of aloe (gADNVs and rADNVs) with higher quality and yield by controlling the final centrifugation time within 20 min, and modulating the viscosity at 2.98 mPa S and 1.57 mPa S respectively. The gADNVs showed great structure and storage stability, antioxidant and antidetergent capacity. They could be efficiently taken up by melanoma cells, and with no toxicity in vitro or in vivo. Indocyanine green (ICG) loaded in gADNVs (ICG/gADNVs) showed great stability in both heating system and in serum, and its retention rate exceeded 90% after 30 days stored in gADNVs. ICG/gADNVs stored 30 days could still effectively damage melanoma cells and inhibit melanoma growth, outperforming free ICG and ICG liposomes. Interestingly, gADNVs showed prominent penetrability to mice skin which might be beneficial to noninvasive transdermal administration. Conclusions Our research was designed to simplify the preparation of drug carrier, and reduce production cost, which provided an alternative for the development of economic and safe drug delivery system. Graphical Abstract

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To overcome the low efficacy of conventional monotherapeutic approaches that use a single drug, functional nanocarriers loaded with an amalgamation of anticancer drugs have been promising in cancer therapy. Herein, aloe-derived nanovesicles (gADNVs) are modified with an active integrin-targeted peptide (Arg-Gly-Asp, RGD) by the postinsertion technique to deliver indocyanine green (ICG) and doxorubicin (DOX) for efficient breast cancer therapy. We presented for the first time that the π−π stacking interaction can turn the "competitive" relationship of ICG and DOX inside gADNVs into a "cooperative" relationship and enhance their loading efficiency. The dual-drug codelivery nanosystem, denoted as DIARs, was well stable and leakproof, exhibiting high tumor-targeting capability both in vitro and in vivo. Meanwhile, this nanosystem showed significant inhibition of cell growth and migration and induced cell apoptosis with the combination of phototherapy and chemotherapy. Intravenous administration of DIARs exhibited high therapeutic efficacy in a 4T1 tumor-bearing mouse model and exhibited no obvious damage to other organs. Overall, our DIAR nanosystem constitutively integrated the natural and economical gADNVs, π−π stacking interaction based on efficient drug loading, and tumor-targeted RGD modification to achieve an effective combination therapy for breast cancer.

Purpose In recent years, a variety of nanoparticles with excellent anticancer and delivery properties have emerged for cancer therapy. However, potential toxicity, high production cost and complex preparation procedures have been obstacles to their use in biomedicine. Here, we obtained cucumber-derived nanovesicles (CDNVs) at high yield and low cost by simple juicing and ultracentrifugation. The anticancer effects of CDNVs were evaluated in vitro and in vivo. Methods Transmission electron microscope, nanoparticle tracking analysis and laser particle size analysis were used to characterize the morphology, diameter and zeta potential of CDNVs, respectively. The anticancer effects of CDNVs in vitro were evaluated by MTT and apoptosis assays. The mechanism was further explored by measuring the protein levels of signal transducer and activator of transcription 3 pathway, reactive oxygen species, cell cycle distribution and caspase activity. In-vivo anticancer efficacy was evaluated by measuring tumor volume and weight of mice in three different treatment groups (CDNVs, cucurbitacin B and PBS). Results CDNVs inhibited proliferation of human non-small cell lung cancer cells by suppressing signal transducer and activator of transcription 3 activation, generating reactive oxygen species, promoting cell cycle arrest, and activating the caspase pathway. These CDNVs exhibited strong anticancer effects both in vitro and in vivo, and reduced the rate of tumor growth without obvious toxicity to mouse visceral organs. Compared with an equivalent dose of cucurbitacin B, CDNVs exerted stronger anticancer effects in vitro and in vivo. Conclusion These results demonstrate that CDNVs suppress tumor growth. This study addresses the development of cancer therapeutic drugs using plant-derived nanovesicles that are cost-efficient, simple to produce in high yields, and provide an alternative approach to drug isolation that may help advance sustainability of medicinal plants.