Traditional drug delivery systems suffer from low drug-loading and relatively weak therapeutic efficacy, therefore, development of new drug delivery systems with high-efficiency has become more urgent. In this report, a novel-innovative drug delivery strategy, namely drug self-framed delivery system (DSFDS), is prepared via using anticancer drugs as polymer frame without using any carriers. The drug molecules (exemplified by doxorubicin) containing more than two nucleophilic functional groups (diols/diamines) directly reacted with hexachlorocyclotriphosphazene via mild precipitation polycondensation under ambient conditions, forming biocompatible drug self-framed delivery nanoparticles. Because of the covalent bonding of the drug molecules, DSFD nanoparticles (DSFDs) with super high drug-loading were stable in the circulation during delivery. However, sustained release of drug in the acidic environment within cells endowed DSFDs with long-term anticancer therapeutic efficacy. This strategy is applicable for diverse hydrophilic and hydrophobic drugs and may be a new platform for designing high drug-loading and release-controllable drug delivery systems.

Despite the burgeoning development and extensive commercialization of sunscreens, challenges remain regarding the biocompatibility and efficacy of commercial sunscreens. Direct exposure to UV filters has given rise to health problems, including the percutaneous penetration and the generation of reactive oxygen species. To address these, we have developed organic UV-filter self-framed microparticles, whereby organic UV-filter molecules self-construct into nanoparticles without any supportive microencapsulation. This approach is unique for its outstanding biocompatibility by reducing the percutaneous penetration of organic UV-filter molecules. Furthermore, the shielding range is extended from the UVB to the entire UV region by the introduction of a physical reflection effect. An in vitro fibroblast culture experiment and the results of in vivo skin protection experiments confirmed their safety. All the experimental results supported the conclusion that sunblock with self-framed microparticles (FSFMPs) has a great potential to become the next generation of UV filters for the UV protection of skin.

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Background Colorectal cancer is known to be resistant to immune checkpoint blockade (ICB) therapy. Sonodynamic therapy (SDT) has been reported to improve the efficacy of immunotherapy by inducing immunogenic cell death (ICD) of cancer. However, the SDT efficacy is extremely limited by Nrf2-based natural redox balance regulation pathway in cancer cells in response to the increased contents of reactive oxygen species (ROS). Nuclear-targeting strategy has shown unique advantages in tumor therapy by directly destroying the DNA. Thus it can be seen that Nrf2-siRNA augmented nuclear-targeting SDT could boost ICB therapy against colorectal cancer. Results The nuclear-targeting delivery system TIR@siRNA (TIR was the abbreviation of assembled TAT-IR780) with great gene carrier capacity and smaller diameter (< 60 nm) was designed to achieve the gene augmented nuclear-targeting SDT facilitating the anti-PD-L1 (programmed cell death-ligand-1) therapy against colorectal cancer. In CT26 cells, TIR@siRNA successfully delivered IR780 (the fluorescent dye used as sonosensitizer) into cell nucleus and Nrf2-siRNA into cytoplasm. Under US (utrasound) irradiation, TIR@siRNA notably increased the cytotoxicity and apoptosis-inducing activity of SDT through down-regulating the Nrf2, directly damaging the DNA, activating mitochondrial apoptotic pathway while remarkably inducing ICD of CT26 cells. In CT26 tumor-bearing mice, TIR@siRNA mediated gene enhanced nuclear-targeting SDT greatly inhibited tumor growth, noticeably increased the T cell infiltration and boosted DPPA-1 peptide-based anti-PD-L1 therapy to ablate the primary CT26 tumors and suppress the intestinal metastases. Conclusions All results demonstrate that TIR@siRNA under US irradiation can efficiently inhibit the tumor progression toward colorectal CT26 cancer in vitro and in vivo by its mediated gene augmented nuclear-targeting sonodynamic therapy. Through fully relieving the immunosuppressive microenvironment of colorectal cancer by this treatment, this nanoplatform provides a new synergistic strategy for enhancing the anti-PD-L1 therapy to ablate colorectal cancer and inhibit its metastasis. Graphical Abstract

Antisense oligodeoxynucleotides (ASODNs) can bind to some specific RNA of survivin can prevent the mRNA translation at the genetic level, which will inhibit survivin expression and make the cancer cells apoptosis. However, the ASODNs-based therapies are hampered by their instability to cellular nuclease and their weak intracellular penetration. Here we reported a calcium phosphate (CP)-based carrier to achieve efficient delivery of ASODNs into cells. In this study, we used a facile microemulsion approach to prepare spherical and porous ASODNs-CP nanoparticles (ASODNS-CPNPs) with the size of 50-70 nm in diameter, and their structure, morphology and composition were characterized by TEM, XRD, FTIR, ICP and DLS, UV-Vis spectroscopy and agarose gel electrophoresis. The results indicated that the nanoparticles have a high ASODNs loading capacity. Furthermore, cellular uptake and delivery efficiency of the ASODNS-CPNPs, as well as cellular apoptosis induced by the ASODNs doping into the calcium phosphate nanoparticles, were investigated by confocal laser scanning microscopy, biological TEM, flow cytometry, and MTT assay. Efficient intracellular delivery of the nanoparticles was observed. All these results suggested that the prepared calcium phosphate nanoparticles could be used as a promising biocarrier for delivery of ASODNs.