Penetration of the blood-brain barrier (BBB) and the blood-brain tumor barrier (BBTB) remains a significant challenge for the delivery of drugs in the treatment of glioma. Therefore, the development of targeted preparations with the ability to penetrate the BBB and BBTB, and target gliomas, is an important approach if we are to improve the efficacy of glioma treatment. In the current study, an active targeting preparation based on PLGA nanoparticles coated with erythrocyte membranes (RBCNPs) and dual-modified with D WSW and NGR peptide ligands (D WSW/NGR-RBCNPs). Euphorbia factor L1 (EFL1) extracted from euphorbiae semen was used as the model drug. The final nanoparticles were characterized by in vivo and in vitro tests. In vitro results showed that EFL1-loaded D WSW/NGR-RBCNPs were taken up by cells and had the ability to penetrate the BBB and BBTB and produce cytotoxic effects. Furthermore, in vivo studies in mice showed that when injected intravenously, these specialized NPs could enter the brain, target tumor tissue, and significantly extend life span. The results showed that dualtargeting EFL1-loaded D WSW/NGR-RBCNPs have significant potential as a nanotherapeutic tool for the treatment of brain glioma.

Background Glioma is one of the deadliest human cancers. Although many therapeutic strategies for glioma have been explored, these strategies are seldom used in the clinic. The challenges facing the treatment of glioma not only involve the development of chemotherapeutic drugs and immunotherapeutic agents, but also the lack of a powerful platform that could deliver these two moieties to the targeted sites. Herein, we developed chemoimmunotherapy delivery vehicles based on C6 cell membranes and DC membranes to create hybrid membrane-coated DTX nanosuspensions (DNS-[C6&DC]m). Results Results demonstrated successful hybrid membrane fusion and nanosuspension functionalization, and DNS-[C6&DC]m could be used for different modes of anti-glioma therapy. For drug delivery, membrane coating could be applied to target the source cancer cells via a homotypic-targeting mechanism of the C6 cell membrane. For cancer immunotherapy, biomimetic nanosuspension enabled an immune response based on the professional antigen-presenting characteristic of the dendritic cell membrane (DCm), which carry the full array of cancer cell membrane antigens and facilitate the uptake of membrane-bound tumor antigens for efficient presentation and downstream immune n. Conclusion DNS-[C6&DC]m is a multifunctional biomimetic nano-drug delivery system with the potential to treat gliomas through tumor-targeted drug delivery combined with immunotherapy, thereby presenting a promising approach that may be utilized for multiple modes of cancer therapy. Graphical Abstract

Nanosuspensions, as a new drug delivery system for insoluble drugs, are only composed of a drug and a small amount of stabilizer, which is dispersed in an aqueous solution with high drug-loading, small particle size, high dispersion, and large specific surface area. It can significantly improve the dissolution, bioavailability, and efficacy of insoluble drugs. In this study, paclitaxel nanosuspensions ((PTX)NS) were prepared by an ultrasonic precipitation method, with the characteristics of simple preparation and easy repetition. With the help of a homologous targeting mechanism, a kind of glioma C6 cancer cell membrane (CCM)-coated (PTX)NS was developed and modified with D WSW peptide to obtain D WSW-CCM-(PTX)NS with the functions of BBB penetration and tumor targeting. The results showed that the cancer cell membrane could effectively camouflage the nanosuspensions so that it was not cleared by the immune system and could cross the blood-brain-barrier (BBB) and selectively target tumor tissues. Cell uptake experiments and in vivo imaging confirmed that the uptake of D WSW-CCM-(PTX)NS by tumor cells and the distribution in intracranial gliomas increased. Cytotoxicity test and in vivo anti-glioma studies showed that D WSW-CCM-(PTX)NS could significantly inhibit the growth of glioma cells and significantly prolong the survival time of glioma-bearing mice. Finally, the cancer cell membrane coating endowed the nanosuspensions with the biological properties of homologous adhesion and immune escape. This study provides an integrated solution for improving the targeting of nanosuspensions and demonstrates the encouraging potential of biomimetic nanosuspensions applicable to tumor therapy.

Effective intracerebral delivery is key for glioma treatment. However, the drug delivery system within the brain is largely limited by its own adverse physical and chemical properties, low targeting efficiency, the blood–brain barrier and the blood–brain tumor barrier. Herein, we developed a simple, safe and efficient biomimetic nanosuspension. The C6 cell membrane (CCM) was utilized to camouflaged the 10-hydroxycamptothecin nanosuspension (HCPT-NS) in order to obtain HCPT-NS/CCM. Through the use of immune escape and homotypic binding of the cancer cell membrane, HCPT-NS/CCM was able to penetrate the blood–brain barrier and target tumors. The HCPT-NS is only comprised of drugs, as well as a small amount of stabilizers that are characterized by a simple preparation method and high drug loading. Similarly, the HCPT-NS/CCM is able to achieve targeted treatment of glioma without any ligand modification, which leads it to be stable and efficient. Cellular uptake and in vivo imaging experiments demonstrated that HCPT-NS/CCM is able to effectively cross the blood–brain barrier and was concentrated at the glioma site due to the natural homing pathway. Our results reveal that the glioma cancer cell membrane is able to promote drug transport into the brain and enter the tumor via a homologous targeting mechanism.

The main treatment measure currently used for glioma treatment is chemotherapy; the biological barrier of solid tumors hinders the deep penetration of nanomedicines and limits anticancer therapy. Furthermore, the poor solubility of many chemotherapeutic drugs limits the efficacy of antitumor drugs. Therefore, improving the solubility of chemotherapeutic agents and drug delivery to tumor tissues through the blood–brain barrier (BBB) and blood–brain tumor barrier (BBTB) are major challenges in glioma treatment. Nanostructured lipid carriers (NLCs) have high drug loading capacity, high stability, and high in vivo safety; moreover, they can effectively improve the solubility of insoluble drugs. Therefore, in this study, we used solvent volatilization and ultrasonic melting methods to prepare dihydroartemisinin nanostructured lipid carrier (DHA-NLC). We further used the glioma C6 cancer cell (CC) membrane to encapsulate DHA-NLC owing to the homologous targeting mechanism of the CC membrane; however, the targeting ability of the CC membrane was weak. We accordingly used targeting ligands for modification, and developed a bionanostructured lipid carrier with BBB and BBTB penetration and tumor targeting abilities. The results showed that DHA-loaded NGR/CCNLC (asparagine–glycine–arginine, NGR) was highly targeted, could penetrate the BBB and BBTB, and showed good anti-tumor effects both in vitro and in vivo , which could effectively prolong the survival time of tumor-bearing mice. Thus, the use of DHA-loaded NGR/CCNLC is an effective strategy for glioma treatment and has the potential to treat glioma.

The excellent adhesion of mussels under wet conditions has inspired the development of numerous catechol-based wet adhesives. Nevertheless, the performance of catechol-based wet adhesive suffers from the sensitivity toward temperature, pH, or oxidation stimuli. Therefore, it is of great significance to develop non-catechol-based wet adhesives to fully recapitulate nature’s dynamic function. Herein, a novel type of non-catechol-based wet adhesive is reported, which is readily formed by self-assembly of commercially available branched polyethylenimine and phosphotungstic acid in aqueous solution through the combination of electrostatic interaction and hydrogen bonding. This wet adhesive shows reversible, tunable, and strong adhesion on diverse substrates and further exhibits high efficacy in promoting biological wound healing. During the healing of the wound, the as-prepared wet adhesive also possesses inherent antimicrobial properties, thus avoiding inflammations and infections due to microorganism accumulation.

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