Melittin, the principal constituent in bee venom, is an attractive candidate for cancer therapy. However, its clinical applications are limited by hemolysis, nonspecific cytotoxicity, and rapid metabolism. Herein, a novel genetically engineered vesicular antibody‐melittin (VAM) drug delivery platform was proposed and validated for targeted cancer combination therapy. VAM generated from the cellular plasma membrane was bio‐synthetically fabricated, with the recombinant protein (hGC33 scFv‐melittin) being harbored and displayed on the cell membrane. The bioactive and targetable nanomelittin conjugated by hGC33 scFv could be released in an MMP14‐responsive manner at tumor sites, which reduced off‐target toxicity, especially the hemolytic activity of melittin. Importantly, VAM could be loaded with small‐molecule drugs or nanoparticles for combination therapy. Nanomelittin formed pores in membranes and disturbed phospholipid bilayers, which allowed the anticancer agents (i.e., chemotherapeutic drug doxorubicin and sonosensitizer purpurin 18 nanoparticles) co‐delivered by VAM to penetrate deeper tumor sites, leading to synergistic therapeutic effects. In particular, the punching effect generated by sonodynamic therapy further improved the immunomodulatory effect of nanomelittin to activate the immune response. Taken together, our findings indicate that clinically translatable VAM‐based strategies represent a universal, promising approach to multimodal synergetic cancer therapy.
In view of the complex procedure of nucleic acid extraction, there exists a huge challenge for the widespread use of point-of-care diagnostics for nucleic acid testing. To achieve point-of-care applications in a more rapid and cost-efficient manner, we designed a snake pipe-shaped microfluidic chip so as to accomplish reagents-prestored, time-saving, operation-simple nucleic acid extraction. All reagents needed for this process, including lysis buffer, wash buffer, elution buffer, and so on, were preloaded in the snake pipe and securely isolated by membrane valves, without the need for using any specialized equipment. By an integrated chip and a powerful ultrasonic, this device could complete virus nucleic acid extraction from sophisticated serum samples in less than 1 min. We used hepatitis B virus (HBV) and human immunodeficiency virus (HIV) mixed with different sources of serum as samples to be extracted. The coefficient of variation of HBV and HIV extraction on-chip was 1.32% and 2.74%, respectively, and there were no significant differences between on-chip and commercial instrument extraction (P > 0.05, α = 0.05) in different dilution ratios, which showed that the extraction device we established had excellent stability and sensitivity.