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Biomaterial-based implants hold great potential for postoperative cancer treatment due to the enhanced drug dosage at the disease site and decreased systemic toxicity. However, the elaborate design of implants to avoid complicated chemical modification and burst release remains challenging. Herein, we report a three-dimensional (3D) printed hydrogel scaffold to enable sustained release of drugs for postoperative synergistic cancer therapy. The hydrogel scaffold is composed of Pluronic F127 and sodium alginate (SA) as well as doxorubicin (DOX) and copper ions (F127-SA/Cu-DOX hydrogel scaffold). Benefiting from the coordination of Cu(II) with both SA and DOX, burst release of DOX can be overcome, and prolonged release time can be achieved. The therapeutic efficiency can be adjusted by altering the amount of DOX and Cu(II) in the scaffolds. Moreover, apoptosis and ferroptosis of cancer cells can be induced through the combination of chemotherapy and chemodynamic therapy. In addition, DOX supplies excess hydrogen peroxide to enhance the efficiency of Cu-based chemodynamic therapy. When implanted in the resection site, hydrogel scaffolds effectively inhibit tumor growth. Overall, this study may offer a new strategy for fabricating local implants with synergistic therapeutic performance for preventing postoperative cancer recurrence.

Lipid-based nanoparticles have made a breakthrough in clinical disease as delivery systems due to their biocompatibility, thermal and long-term stability, high loading ability, simplicity of preparation, inexpensive production costs, and scalable manufacturing production. In particular, during the COVID-19 pandemic, this delivery system served as a vital vaccine component for virus confrontation. To obtain effective drug delivery, lipid-based nanoparticles should reach the desired sites with high efficiency, enter target cells, and release drugs. The structures and compositions of lipid-based nanoparticles can be modified to regulate these behaviors in vivoto enhance the therapeutic effects. Herein, we briefly review the development of lipid-based nanoparticles, from simple self-assembled nanovesicle-structured liposomes to multifunctional lipid nanoparticles. Subsequently, we summarize the strategies that regulate their tissue distribution, cell internalization, and drug release, highlighting the importance of the structural and componential design. We conclude with insights for further research to advance lipid-based nanotechnology.

In mouse peritoneal and other serous cavities, the transcription factor GATA6 drives the identity of the major cavity resident population of macrophages, with a smaller subset of cavity-resident macrophages dependent on the transcription factor IRF4. Here we showed that GATA6+macrophages in the human peritoneum were rare, regardless of age. Instead, more human peritoneal macrophages aligned with mouse CD206+LYVE1+cavity macrophages that represent a differentiation stage just preceding expression of GATA6. A low abundance of CD206+macrophages was retained in C57BL/6J mice fed a high-fat diet and in wild-captured mice, suggesting that differences between serous cavity-resident macrophages in humans and mice were not environmental. IRF4-dependent mouse serous cavity macrophages aligned closely with human CD1c+CD14+CD64+peritoneal cells, which, in turn, resembled human peritoneal CD1c+CD14−CD64−cDC2. Thus, major populations of serous cavity-resident mononuclear phagocytes in humans and mice shared common features, but the proportions of different macrophage differentiation stages greatly differ between the two species, and dendritic cell (DC2)-like cells were especially prominent in humans.

Mesenchymal stem cell (MSC) has been increasingly applied to cancer therapy because of its tumor-tropic capability. However, short retention at target tissue and limited payload option hinder the progress of MSC-based cancer therapy. Herein, we proposed a hybrid spheroid/nanomedicine system, comprising MSC spheroid entrapping drug-loaded nanocomposite, to address these limitations. Spheroid formulation enhanced MSC’s tumor tropism and facilitated loading of different types of therapeutic payloads. This system acted as an active drug delivery platform seeking and specifically targeting glioblastoma cells. It enabled effective delivery of combinational protein and chemotherapeutic drugs by engineered MSC and nanocomposite, respectively. In an in vivomigration model, the hybrid spheroid showed higher nanocomposite retention in the tumor tissue compared with the single MSC approach, leading to enhanced tumor inhibition in a heterotopic glioblastoma murine model. Taken together, this system integrates the merits of cell- and nanoparticle- mediated drug delivery with the tumor-homing characteristics of MSC to advance targeted combinational cancer therapy.