Advances in Peptide Functionalization on Mesoporous Silica Nanoparticles for Controlled Drug Release.

During the last decade, using versatile, promising, and fascinating mesoporous silica nanoparticles (MSNs) as site-specific and stimuli-responsive drug delivery systems (DDSs) has received concentrated research interest. As one of the most attractive surface modification units, peptides have inherent bioactivity, biodegradability and biocompatibility. Recent progresses in the utilization of versatile peptides for surface functionalization of MSNs to achieve cell-specific targeting, fluorescence imaging, and intracellular diagnosis and treatment of tumors are summarized in this review. The various functional peptides decorated on the MSNs are introduced and classified into three types, including targeting peptides, stimuli-responsive peptides and multifunctional chimeric peptides. The limitations and challenges of peptide modified MSNs and their potential applications are further discussed.

Self-Guiding Polymeric Prodrug Micelles with Two Aggregation-Induced Emission Photosensitizers for Enhanced Chemo-Photodynamic Therapy.

Nowadays, aggregation-induced emission luminogens (AIEgens) with reactive oxygen species (ROS) generating ability have been used as photosensitizers for imaging guided photodynamic therapy (PDT). To achieve enhanced antitumor outcomes, combining AIEgens-based PDT with chemotherapy is an efficient strategy. However, the therapeutic efficiency is hampered by the limited cellular uptake efficiency and the appropriate light irradiation occasion. In this paper, a self-guiding polymeric micelle (TB@PMPT) composed of two AIE photosensitizers and a reduction-sensitive paclitaxel prodrug (PTX-SS-N3) was established for enhanced chemo-photodynamic therapy by a dual-stage light irradiation strategy. When the micelles were accumulated in tumor tissues, the first light irradiation (L1, 6 min) was utilized to facilitate cellular uptake by "photochemical internalization" (PCI). Then, the intracellular glutathione (GSH) would induce the PTX release, micelles disassembly and the aggregation state change of AIEgens. The fluorescence signal change of two AIEgens-based ratiometric fluorescent probe could not only precisely guide the second light irradiation (L2, 18 min) for sufficient ROS production, but also monitor the nonfluorescent drug PTX release in turn. Both in vivo and in vitro studies demonstrated that the dual-stage light irradiation strategy employed for TB@PMPT micelles exhibited a superior therapeutic effect over only 24 min continuous light irradiation.

Nanococktail Based on AIEgens and Semiconducting Polymers: A Single Laser Excited Image-Guided Dual Photothermal Therapy.

Semiconducting polymers (SPs)-based dual photothermal therapy (PTT) obtained better therapeutic effect than single PTT due to its higher photothermal conversion efficiency. However, most dual PTT need to use two lasers for heat generation, which brings about inconvenience and limitation to the experimental operations. Herein, we report the development of "nanococktail" nanomaterials (DTPR) with 808 nm-activated image-guided dual photothermal properties for optimized cancer therapy. Methods: In this work, we co-encapsulated AIEgens (TPA-BDTO, T) and SPs (PDPPP, P) by using maleimide terminated amphiphilic polymer (DSPE-PEG2000-Mal, D), then further conjugated the targeting ligands (RGD, R) through "click" reaction. Finally, such dual PTT nanococktail (termed as DTPR) was constructed. Results: Once DTPR upon irradiation with 808 nm laser, near-infrared fluorescence from T could be partially converted into thermal energy through fluorescence resonance energy transfer (FRET) between T and P, coupling with the original heat energy generated by the photothermal agent P itself, thus resulting in image-guided dual PTT. The photothermal conversion efficiency of DTPR reached 60.3% (dual PTT), much higher as compared to its inherent photothermal effect of only 31.5% (single PTT), which was further proved by the more severe photothermal ablation in vitro and in vivo upon 808 nm laser irradiation. Conclusion: Such smart "nanococktail" nanomaterials could be recognized as a promising photothermal nanotheranostics for image-guided cancer treatment.

Longitudinal pattern of early maturation on morning cortisol and depressive symptoms: Sex-specific effects.

There is still insufficient understanding of the underlying processes that contribute to internalizing problems of early maturing adolescents. The purpose of this study is to examine the longitudinal pattern of early maturation and its effects on morning cortisol and depressive symptoms among a general population of adolescent cohort aged 8-11 years old at baseline (boys=424, girls=288). Results suggest newly-onset early maturation boys have 3-times more likely to have depressive symptoms at 1-year follow-up (adjusted odds ratio=3.197, 95% confidence interval=1.595-6.405); while in girls, stable early maturation individuals are more than 4 times as likely to have depressive symptoms (adjusted odds ratio=4.566, 95% confidence interval=1.882-11.077). Morning cortisol has moderating effects in the association of depressive symptoms with newly-onset early maturation in boys and stable early maturation in girls. These findings possibly explain current inconsistent results regarding association between earlier maturation and risk of depression in adolescents. Further longitudinal studies are needed to explore HPG-HPA interactions in adolescence, which may be critical to understanding the heightened susceptibility of mental health problems.