Table 1 Carrier-mediated combination of chemotherapy drugs and cytokines
| Carrier design (Structure/Injection route) | Chemotherapy agent | Cytokines | Tumor type | Synergic actions and advantages of NPs in the combination | Refs. |
|---|---|---|---|---|---|
| Polymeric NPs (TMC/SC) | DOX | rhIL-2 | Hepatic tumor |
Protection of rhIL-2 from enzymolysis without any damage on its bioactivity Considerable inhibition of tumor growth and enhancement of IgG and CTLs levels compared with free drug | [142] |
| Hybrid NPs (Lipid coated MSNs/IV) | ATRA + IL-2 | Melanoma |
Enhancement of anti-tumor efficacy and considerable delay in tumor growth and metastasis Activation of TILs and NK cells Induction of IL-12 and IFN-γ secretion and downregulation of MDSCs, IL-10, and TGF-β | [120] | |
| Polymeric NPs (PLGA as core and PEO–PPO–PEO as shell/IV) | IFN-γ |
Excellent synergistic anti-tumor efficiency Activation of CD4+ T cells, CTLs, and NK cells Induction of IL-2 and TNF-α secretion and downregulation of expression of IL-10 and TGF-β | [143] | ||
| Hydrogel NPs (PELG-PEG-PELG) | IL-2 + IFN-γ |
Increased anti-tumor efficacy toward free drugs due to sustained release of drugs Increased proliferation of CD3+/CD8+ and CD3+/CD4+ T cells | [144] | ||
| Cell-derived nanovesicles (DC 2.4/IV) | IL-2, IL-2 + IFN-γ | Melanoma and breast cancer |
Efficient inhibition of primary 4T1 tumor progression and lung metastasis of breast cancer Enhancement of DC maturation, promotion of infiltration and activation of CD8+ cells and NK cells Increase in recruitment of Ly6G+ neutrophils and CD45+ immune cells | [145] | |
| Nanogels (PPLG and HPCS/PPLL/SC) | rhIL-2 + rhIFN-γ | NSCLC and breast cancer |
Prolonged and continuous release of payloads Significant inhibition of tumor cell proliferation Synergistic anti-cancer efficacy via regulation of apoptosis-related genes in xenograft tumor-bearing mice | [146] | |
| Polymeric NPs (PLGA-mPEG-PLGA/IV) | PTX | IL-2 | Melanoma |
Remarkable inhibition of tumor growth and metastasis Prolonged overall survival of treated mice in comparison to chemotherapy or cytokine therapy alone Promotion of tumor immunogenicity and the anti-tumor response of immune cells | [147] |
| Nanogels (Erythrocyte membrane coated nanogels/IV) | Metastatic melanoma (lung metastasis) |
Extended in vivo circulation time Increase in anti-tumor activity and improvement in lung metastasis inhibition of PTX/IL-2 loaded nanogel compared to PTX or IL-2 loaded nanogel alone Decrease in number of immune-suppressive cells and enhancement of immune effector cells in the TME | [148] | ||
| Polymeric NPs (mPEG-PDLLA as core and pluronic F127 as shell/IV) | IL-12 | Breast cancer |
Significant accumulation of NPs in tumor cells because of their acid-sensitive property Activation of immune effector cells like T cells and NK cells Modulation of the immunosuppressive TME by inhibiting TregS and inducing differentiation of M1-type MQs Prolonged survival of tumor-bearing mice | [149] | |
| Polymeric hydrogels (mPEG-b-PELG-based hydrogels/SC) | CDDP | IL-15 | Melanoma |
Inducing cell cycle arrest, synergistic anti-cancer efficacy, and reduced systemic toxicity compared to monotherapy Enhanced anti-tumor immunity owing to suppression of TregS and activation of NK cells and CTLs | [150] |