Nanoparticles have been widely used in tumor targeted drug delivery, while the antitumor effects are not always satisfactory due to the limited penetration and retention. As we all know, there is a paradox that nanoparticles with large sizes tend to distribute around tumor blood vessels rather than penetrate into tumor parenchyma, while smaller sizes can penetrate deeply but with poor tumor retention. In recent days, an intelligent, size-tunable strategy provided a solution to determine the size problem of nanoparticles and exhibited good application prospects. In this review, we summarize series of stimuli-induced aggregation and shrinkage strategies for tumor targeted drug delivery, which can significantly increase the retention and penetration of nanodrugs in tumor sites at the same time, thus promoting treatment efficacy. Internal (enzymes, pH, and redox) and external (light and temperature) stimuli are introduced to change the morphology of the original nanodrugs through protonation, hydrophobization, hydrogen bond, π−π stacking and enzymolysis-resulted click reactions or dissociation, etc. Apart from applications in oncotherapy, size-tunable strategies also have a great prospect in the diagnosis and real time bioimaging fields, which are also introduced in this review. Finally, the potential challenges for application and future directions are thoroughly discussed, providing guidance for further clinical transformation.

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The objective of this study was to investigate the associations between selenium exposure and cancer risk. We identified 69 studies and applied meta-analysis, meta-regression and dose-response analysis to obtain available evidence. The results indicated that high selenium exposure had a protective effect on cancer risk (pooled OR = 0.78; 95%CI: 0.73–0.83). The results of linear and nonlinear dose-response analysis indicated that high serum/plasma selenium and toenail selenium had the efficacy on cancer prevention. However, we did not find a protective efficacy of selenium supplement. High selenium exposure may have different effects on specific types of cancer. It decreased the risk of breast cancer, lung cancer, esophageal cancer, gastric cancer, and prostate cancer, but it was not associated with colorectal cancer, bladder cancer, and skin cancer.

Glioma treatment using targeted chemotherapy is still far from satisfactory due to not only the limited accumulation but also the multiple survival mechanisms of glioma cells, including up-regulation of both autophagy and programmed cell death ligand 1 (PD-L1) expression. Herein, we proposed a combined therapeutic regimen based on functional gold nanoparticles (AuNPs)-enabled chemotherapy, autophagy inhibition, and blockade of PD-L1 immune checkpoint. Specifically, the legumain-responsive AuNPs (D&H-A-A&C) could passively target the glioma site and form in situ aggregates in response to legumain, leading to enhanced accumulation of doxorubicin (DOX) and hydroxychloroquine (HCQ) at the glioma site. HCQ could inhibit the DOX-induced cytoprotective autophagy and thus resensitize glioma cells to DOX. Parallelly, inhibiting autophagy could also inhibit the formation of autophagy-related vasculogenic mimicry (VM) by glioma stem cells. In vivo studies demonstrated that D&H-A-A&C possessed promising antiglioma effect. Moreover, cotreatment with anti-PD-L1 antibody was able to neutralize immunosuppressed glioma microenvironment and thus unleash antiglioma immune response. In vivo studies showed D&H-A-A&C plus anti-PD-L1 antibody could further enhance antiglioma effect and efficiently prevent recurrence. The effectiveness of this strategy presents a potential avenue to develop a more effective and more personalized combination therapeutic regimen for glioma patients.