A Coupling-Induced Assembly Strategy for Constructing Artificial Shell on Mitochondria in Living Cells.

The strategy of in vivo self-assembly has been developed for improved enrichment and long-term retention of anticancer drug in tumor tissues. However, most self-assemblies with non-covalent bonding interactions are susceptible to complex physiological environments, leading to weak stability and loss of biological function. Here, we develop a coupling-induced assembly (CIA) strategy to generate covalently crosslinked nanofibers, which is applied for in situ constructing artificial shell on mitochondria. The oxidation-responsive peptide-porphyrin conjugate P1 is synthesized, which self-assemble into nanoparticles. Under the oxidative microenvironment of mitochondria, the coupling of thiols in P1 causes the formation of dimers, which is further ordered and stacked into crosslinked nanofibers. As a result, the artificial shell is constructed on the mitochondria efficiently through multivalent cooperative interactions due to the increased binding sites. Under ultrasound (US) irradiation, the porphyrin molecules in the shell produce a large amount of reactive oxygen species (ROS) that act on the adjacent mitochondrial membrane, exhibiting ~2-fold higher antitumor activity than nanoparticles in vitro and in vivo. Therefore, the mitochondria-targeted CIA strategy provides a novel perspective on improved sonodynamic therapy (SDT) and shows potential applications in antitumor therapies.

In Vivo Self-Assembly Induced Cell Membrane Phase Separation for Improved Peptide Drug Internalization.

Therapeutic peptides have been widely concerned, but their efficacy is limited by the inability to penetrate cell membranes, which is a key bottleneck in peptide drugs delivery. Herein, an in vivo self-assembly strategy is developed to induce phase separation of cell membrane that improves the peptide drugs internalization. A phosphopeptide KYp is synthesized, containing an anticancer peptide [KLAKLAK]2 (K) and a responsive moiety phosphorylated Y (Yp). After interacting with alkaline phosphatase (ALP), KYp can be dephosphorylated and self-assembles in situ, which induces the aggregation of ALP and the protein-lipid phase separation on cell membrane. Consequently, KYp internalization is 2-fold enhanced compared to non-responsive peptide, and IC50 value of KYp is approximately 5 times lower than that of free peptide. Therefore, the in vivo self-assembly induced phase separation on cell membrane promises a new strategy to improve the drug delivery efficacy in cancer therapy.

Self-Assembly of Peptides as an Alluring Approach toward Cancer Treatment and Imaging.

Cancer is a severe threat to humans, as it is the second leading cause of death after cardiovascular diseases and still poses the biggest challenge in the world of medicine. Due to its higher mortality rates and resistance, it requires a more focused and productive approach to provide the solution for it. Many therapies promising to deliver favorable results, such as chemotherapy and radiotherapy, have come up with more negatives than positives. Therefore, a new class of medicinal solutions and a more targeted approach is of the essence. This review highlights the alluring properties, configurations, and self-assembly of peptide molecules which benefit the traditional approach toward cancer therapy while sparing the healthy cells in the process. As targeted drug delivery systems, self-assembled peptides offer a wide spectrum of conjugation, biocompatibility, degradability-controlled responsiveness, and biomedical applications, including cancer treatment and cancer imaging.

[Factors associated with retention in a community-based methadone maintenance treatment among heroin addicts].

OBJECTIVE: To explore factors associated with retention in a community-based methadone maintenance treatment (MMT) among heroin addicts in Xichang of Sichuan province. METHODS: All 206 heroin addicts were first admitted to MMT community-based program between March to September 2004. Baseline data of patients characteristics, social function, drug using behaviors, sexual behaviors, dose of methadone and retention were collected. RESULTS: Up to Oct, 2005, all 206 patients contributed 8.98 +/- 5.74 person-months of following-up. The retention rates were 58.7% after 6 months and 34.6% after 12 months respectively. Cox proportional hazard regression model indicated that the employed (HR, 0.60; 95% CI, 0.39 - 0.92), helping family to do housework in past 30 days more than once a day (HR, 0.59; 95% CI, 0.42 - 0.82) and previous self-detoxification > or = 3 times (HR, 0.65; 95% CI, 0.47 - 0.91) were independently associated with retention. CONCLUSION: We should give individual counseling to help heroin addicts increasing compliance.

[A prospective cohort study on human immunodeficiency virus and syphilis seroconversion among injecting drug users].

OBJECTIVE: To study the rate of human immunodeficiency virus (HIV) seroconversion, HIV transmission and related risk factors among injecting drug users (IDUs) in an area of Sichuan province. METHODS: In November 2002, a community-based baseline survey was conducted to recruit 333 HIV-seronegative IDUs for a prospective cohort study in Xichang county of Sichuan province, China. Follow-up visits were carried out every 6 months to study the situation of drug use, sexual behaviors of the IDUs and blood specimens were collected to test for antibodies against HIV and syphilis. RESULTS: During a 24-month follow-up period, cohort retention rate and HIV incidence were 75.7% and 2.53 per 100 person-years [95% confidence interval (CI): 1.10-3.97)], respectively. Multivariate Poisson regression model showed that risk factors which were significantly associated with HIV seroconversion would include: ethnicity (RR = 12.42; 95% CI: 2.72-56.74, P = 0.0012) and needle or syringe sharing in the past 3 months (RR = 4.06; 95% CI: 1.29-12.81, P = 0.0168). Syphilis seroconversion in this cohort was 4.71 per 100 person-years (95% CI: 2.59-6.82). In multivariate Poisson regression being female (RR = 4.42; 95% CI: 1.78-10.99, P = 0.0014) appeared to be the only factor which was significantly associated with syphilis seroconversion. CONCLUSION: Our study results showed that there was a rapid transmission of HIV and syphilis among IDUs in Sichuan province, suggesting that effective intervention should be urgently taken.