Background: According to data estimated by the WHO, primary liver cancer is currently the fourth most common malignant tumor and the second leading cause of death around the world. Hepatocellular carcinoma (HCC) is one of the most common primary liver malignancies, so effective therapy is highly desired for HCC. Results: In this study, the use of poly(l-Aspartic acid)-poly(ethylene glycol)/combretastatin A4 (CA4-NPs) was aimed to significantly disrupt new blood vessels in tumor tissues for targeted hepatic tumor therapy. Here, PEG-b-PAsp-g-CA4 showed significantly prolonged retention in plasma and tumor tissue. Most importantly, CA4-NPs were mainly distributed at the tumor site because of the triple target effects—enhanced permeability and retention (EPR) effect, acid-sensitive (pH = 5.5) effect to the tumor microenvironment (TME), and good selectivity of CA4 for central tumor blood vessel. Considering that CA4-NPs might induce severe hypoxic conditions resulting in high expression of HIF-1α in tumor tissues, which could induce the overexpression of PD-L1, herein we also used a programmed death-ligand 1 antibody (aPD-L1) to prevent immunosuppression. This way of complementary combination is able to achieve an ideal treatment effect in tumor site where CA4-NPs and aPD-L1 could respond to the inner area and peripheral area, respectively. As a result, a significant decrease in tumor volume and weight was observed in the combination group of CA4-NPs plus aPD-L1 compared with CA4-NPs or aPD-L1 monotherapy in subcutaneous Hepa1-6 hepatic tumor models. Conclusions: We presented a new idea that co-administration of CA4-NPs and aPD-L1 possessed notable anti-tumor efficacy for HCC treatment. Graphic

Biomolecule-based coordination complex nanoassemblies are a new type of functional materials that are attracting increasing attention. They could possess functionalities that are not readily attainable with other materials, and represent a promising research area that can be exploited in coordination chemistry and materials science. Using bioactive folic acid molecule as a linker, Ni–folate–hydrazine coordination complex nanotubes (CCNTs) have been effectively constructed using the solvothermal method. This is not only the first example of the CCNTs being formed using a nonpyridyl-based molecule as a linker, but also the first report on biomolecule-based CCNTs (BMB-CCNTs) with anticancer activity. It does not require any post treatment to achieve targeted delivery and biocompatible performance. The BMB-CCNTs are sufficiently stable at normal pH of 7.4 until it enters a tumor cell, subsequently it breaks open to release drug in the tumor cell. Furthermore, it overcomes the major limitations of antibody–drug and folate–drug conjugates and is a potential smart multi-functional nanomedicine system. The results of in vitro cytotoxicity assay reveal that the antitumor ability of BMB-CCNTs is similar to cisplatin (CDDP), while their cytotoxicity for normal cells is lower than the latter. Furthermore, BMB-CCNTs exhibit excellent performance as drug carriers and target agents for delivering drugs into tumor cells. Bio-TEM and confocal laser scanning microscope images trace the uptake process of CDDP-CCNTs by a tumor cell. CDDP-CCNTs exhibit dual anti-cancer effect.

A pH-sensitive drug delivery system of HSNPs sealed with ZnO QDs nanocarrier, where the HSNPs have the large hollow interiors for delivering hydrophobic camptothecin and the mesoporous structure for delivering hydrophilic doxorubicin.

Dendritic cells (DCs) based cancer immunotherapy is largely dependent on adequate antigen delivery and efficient induction of DCs maturation to produce sufficient antigen presentation and ultimately lead to substantial activation of tumor-specific CD8⁺ T cells. Carbon nanotubes (CNTs) have attracted great attention in biomedicine because of their unique physicochemical properties. In order to effectively deliver tumor antigens to DCs and trigger a strong anti-tumor immune response, herein, a specific DCs target delivery system was assembled by using multi-walled carbon nanotubes modified with mannose which can specifically bind to the mannose receptor on DCs membrane. Ovalbumin (OVA) as a model antigen, could be adsorbed on the surface of mannose modified multi-walled carbon nanotubes (Man-MWCNTs) with a large drug loading content. This nanotube-antigen complex showed low cytotoxicity to DCs and was efficiently engulfed by DCs to induce DCs maturation and cytokine release in vitro, indicating that it could be a potent antigen-adjuvant nanovector of efficient antigen delivery for therapeutic purpose.