For
systemic delivery of small interfering RNA (siRNA) to solid
tumors, the carrier must circulate avoiding premature degradation,
extravasate and penetrate tumors, enter target cells, traffic to the
intracellular destination, and release siRNA for gene silencing. However,
existing siRNA carriers, which typically exhibit positive charges,
fall short of these requirements by a large margin; thus, systemic
delivery of siRNA to tumors remains a significant challenge. To overcome
the limitations of existing approaches, we have developed a carrier
of siRNA, called “Nanosac”, a noncationic soft polyphenol
nanocapsule. A siRNA-loaded Nanosac is produced by sequential coating
of mesoporous silica nanoparticles (MSNs) with siRNA and polydopamine,
followed by removal of the sacrificial MSN core. The Nanosac recruits
serum albumin, co-opts caveolae-mediated endocytosis to enter tumor
cells, and efficiently silences target genes. The softness of Nanosac
improves extravasation and penetration into tumors compared to its
hard counterpart. As a carrier of siRNA targeting PD-L1, Nanosac induces
a significant attenuation of CT26 tumor growth by immune checkpoint
blockade. These results support the utility of Nanosac in the systemic
delivery of siRNA for solid tumor therapy.
This meta-analysis aims to evaluate the trend, methodological quality and completeness of studies on intracellular delivery of antimicrobial agents. PubMed, Embase, and reference lists of related reviews were searched to identify original articles that evaluated carrier-mediated intracellular delivery and pharmacodynamics (PD) of antimicrobial therapeutics against intracellular pathogens in vitro and/or in vivo. A total of 99 studies were included in the analysis. The most commonly targeted intracellular pathogens were bacteria (62.6%), followed by viruses (16.2%) and parasites (15.2%). Twenty-one out of 99 (21.2%) studies performed neither microscopic imaging nor flow cytometric analysis to verify that the carrier particles are present in the infected cells. Only 31.3% of studies provided comparative inhibitory concentrations against a free drug control. Approximately 8% of studies, albeit claimed for intracellular delivery of antimicrobial therapeutics, did not provide any experimental data such as microscopic imaging, flow cytometry, and in vitro PD. Future research on intracellular delivery of antimicrobial agents needs to improve the methodological quality and completeness of supporting data in order to facilitate clinical translation of intracellular delivery platforms for antimicrobial therapeutics.
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