Although notable progress has been made on novel cancer treatments, the overall survival rate and therapeutic effects are still unsatisfactory for cancer patients. Chemoimmunotherapy, combining chemotherapeutics and immunotherapeutic drugs, has emerged as a promising approach for cancer treatment, with the advantages of cooperating two kinds of treatment mechanism, reducing the dosage of the drug and enhancing therapeutic effect. Moreover, nano-based drug delivery system (NDDS) was applied to encapsulate chemotherapeutic agents and exhibited outstanding properties such as targeted delivery, tumor microenvironment response and site-specific release. Several nanocarriers have been approved in clinical cancer chemotherapy and showed significant improvement in therapeutic efficiency compared with traditional formulations, such as liposomes (Doxil®, Lipusu®), nanoparticles (Abraxane®) and micelles (Genexol-PM®). The applications of NDDS to chemoimmunotherapy would be a powerful strategy for future cancer treatment, which could greatly enhance the therapeutic efficacy, reduce the side effects and optimize the clinical outcomes of cancer patients. Herein, the current approaches of cancer immunotherapy and chemoimmunotherapy were discussed, and recent advances of NDDS applied for chemoimmunotherapy were further reviewed.
Doping in semiconductors is a fundamental issue for developing high performance devices. However, the doping behavior in Si nanocrystals (Si NCs) has not been fully understood so far. In the present work, P-doped Si NCs/SiO2 multilayers are fabricated. As revealed by XPS and ESR measurements, P dopants will preferentially passivate the surface states of Si NCs. Meanwhile, low temperature ESR spectra indicate that some P dopants are incorporated into Si NCs substitutionally and the incorporated P impurities increase with the P doping concentration or annealing temperature increasing. Furthermore, a kind of defect states will be generated with high doping concentration or annealing temperature due to the damage of Si crystalline lattice. More interestingly, the incorporated P dopants can generate deep levels in the ultra-small sized (~2 nm) Si NCs, which will cause a new subband light emission with the wavelength compatible with the requirement of the optical telecommunication. The studies of P-doped Si NCs/SiO2 multilayers suggest that P doping plays an important role in the electronic structures and optoelectronic characteristics of Si NCs.
The specific-targeting approach could promote the specificity of diagnosis and the accuracy of cancer treatment. The choice of a specific-targeting receptor is the key step in this approach. Glypican-3 (GPC3) is an oncofetal proteoglycan anchored on the cell membrane. It is overexpressed even in the early stage of hepatocellular carcinoma (HCC), whereas it shows almost no expression in the healthy adult liver. Therefore, GPC3 may be applied as a specific-targeting receptor for HCC theranostics. In this study, a GPC3 specific-targeting theranostics nanodevice, GPC3 targeting peptide (named G12)-modified liposomes co-loaded with sorafenib (SF) and IR780 iodide (IR780), was developed (GSI-Lip), which aims to realize early diagnosis and precise chemo-photothermal therapy of HCC. SF was the first-line chemotherapy drug for the treatment of HCC. IR780 was used for photothermal therapy and near-infrared fluorescence imaging. The evaluation of early diagnosis verified that early-stage tumors (3.45 ± 0.98 mm3, 2 days after 5 × 105 H22 cells’ inoculation in mice) could be clearly detected using GSI-Lip, which was significantly more sensitive than folic acid-modified liposomes (p < 0.01, 32.90 ± 10.01 mm3, 4 days after 1 × 106 H22 cells’ inoculation in mice). The study of the endocytic pathway indicated that specific G12/GPC3 recognition may induce caveolae-mediated endocytosis of GSI-Lip. Notably, the accumulation of GSI-Lip in tumors was significantly increased compared with that observed with folic acid-modified liposomes (p < 0.01). Specific-targeting endowed the precise antitumor effect of GSI-Lip. GSI-Lip showed a higher antitumor efficacy in comparison with folic acid-modified liposomes (inhibition rate: 90.52% vs 84.22%, respectively; p < 0.01). During a period of 21 days, the synergistic chemo-photothermal therapy (GSI-Lip + laser) exhibited a better antitumor effect versus GSI-Lip without laser (inhibition rate: 94.93% vs 90.52%, respectively; p < 0.01). Overall, GPC3-targeted GSI-Lip promoted the sensitivity and specificity of HCC early diagnosis and achieved synergistic efficacy of chemo-photothermal theranostics, which has potential clinical applications. Furthermore, the present study revealed that a more specific-targeting ligand could further improve the efficacy of theranostics against HCC.
Cell therapy is a promising strategy for cancer therapy. However, its therapeutic efficiency remains limited due to the complex and immunosuppressive nature of tumor microenvironments. In this study, the “cell-chemotherapy” strategy was presented to enhance antitumor efficacy. M1-type macrophages, which are therapeutic immune cells with both of immunotherapeutic ability and targeting ability, carried sorafenib (SF)-loaded lipid nanoparticles (M1/SLNPs) were developed. M1-type macrophages were used both as therapeutic tool to provide immunotherapy and as delivery vessel to target deliver SF to tumor tissues for chemotherapy simultaneously. M1-type macrophages were obtained by polarizing macrophages using lipopolysaccharide, and M1/SLNPs were obtained by incubating M1-type macrophages with SLNP. Tumor accumulation of M1/SLNP was increased compared with SLNP (p < 0.01), which proved M1/SLNP could enhance tumor targeting of SF. An increased ratio of M1-type macrophages to M2-type macrophages, and the CD3+CD4+ T cells and CD3+CD8+ T cell quantities in tumor tissues after treatment with M1/SLNP indicated M1/SLNP could relieve the immunosuppressive tumor microenvironments. The tumor volumes in the M1/SLNP group were significantly smaller than those in the SLNP group (p < 0.01), indicating M1/SLNP exhibited enhanced antitumor efficacy. Consequently, M1/SLNP showed great potential as a novel cell-chemotherapeutic strategy combining both cell therapy and targeting chemotherapy.
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