Table 2 Carrier-mediated combination of chemotherapy drugs and immune adjuvants
| Carrier design (Structure/injection route) | Chemotherapy agent | Immune adjuvants | Tumor type | Synergic actions and advantages of NPs in the combination | Refs. |
|---|---|---|---|---|---|
| Hybrid NPs (G4-Arga/PLGA-PEG-PLGA hydrogel/IV) | DOX | L-Arg | Breast cancer |
High therapeutic efficacy and great tumor growth inhibition in 4T1 cells-xenografted mice Synergistic immune therapy through the production of NO by providing a substrate (L-Arg) of iNOS in MQs | [151] |
| Lipid NPs (TH peptide-modified liposomes/IV) | PTX | αGC + PD-L1 (not encapsulated in NP) | Melanoma and lung metastasis |
Upregulation of IFN-γ, maturation of DCs, and activation of NKT cells Significant anti-metastatic effect, enhanced CTL responses, and prolonged survival | [152] |
| αGC + acetyl-CoA ACAT-1 inhibitor avasimibe (not encapsulated in NP) |
Inhibition of growth and metastasis of melanoma tumors Promotion of the anti-tumor effect via stimulation of CTL responses and formation of TCR Induction of apoptosis through inhibition of ACAT-1 due to an increase in free cholesterol level | [153] | |||
| Polymeric NPs (PLGA/Peritumoral) | TLR4 agonist, P-LPS | Melanoma |
Increased anti-tumor immune response at the TME compared to PTX and P-LPS alone Activation of APCs and T cells in the tumor site and induction of Th1 immune response Enhancement of TNF-α, IFN-γ, and IL-12 secretion Increase in the infiltration of MQs, DCs, and CD4+ and CD8+ T lymphocytes | [154] | |
| Polymeric NPs (PLGA/IV) | TLR4 agonist, SP-LPS | Melanoma and MQ model |
High amount of PTX in tumor mass compared to commercial PTX followed by IV injection High anti-cancer activity and anti-tumor immune responses Activation of MQs and effector immune cells like cytotoxic T cells and NK cells in splenocytes Secretion of various PICs such as IL-12 and TNF-α | [155] | |
|
Hybrid NPs (Conjugate of PTX and SP-LPS/IV) | TLR4 agonist, SP-LPS |
Improvement in anti-tumor activity Enhanced percentage of activated immune cells such as MQs, especially M1 type and Th cells Increasing the secretion of IFN-γ, IL-12, and TNF-α | [156] | ||
| Polymeric NPs (PEG-PEI/Tail vein) | DOX | TLR2 agonist, Zymosan | Breast cancer |
Accumulation of NPs in hypoxic regions of the tumor Inhibition of tumor progression and metastasis, and induction of greater apoptosis Modulation of TAMs differentiation and an increase in expression of Th1 specific cytokines Decrease in VEGFR2 expression and facilitation of anti-angiogenic effect | [157] |
| Hybrid NPs (MS-Zn micro-rosettes/IV) | Poly I:C sodium salt | Bilateral LLC cell inoculation model |
Effective inhibition of tumor growth at the local site Prevention of distant tumor metastases Increased IFN-γ secretion and CD4+ and CD8+ T cell populations | [127] | |
| Polymeric NPs (PLGA-PEG/IV) | TLR3 agonist, poly I:C + Resiquimod (R848) immune adjuvant + CCL20 chemokine | Lung carcinoma and colon adenocarcinoma |
Excellent combination therapeutic efficacy compared to monotherapy Longer survival rate in treated mice Strong activation of specific CTLs in the TME and blood circulation | [158] | |
| Hybrid NPs (Aptamer-G4 PAMAM bioconjugate/IV) | TLR9 agonist, CpG ODN | Prostate cancer |
Excellent anti-tumor efficacy and tumor size reduction in mice treated with combination therapy compared to free DOX treated group Higher levels of the IL-1β, IL-12, IL-6, and TNF-α cytokines in MQ cells | [159] | |
| Biomimetic NPs (HDL mimicking/IV) | Aptamer-CpG fused sequences (Apt-CpG-DSPE) | Lung cancer |
Enhancement of M1 (MQs) switched the immune-suppressive TME to the immunostimulatory one Facilitation of cell apoptosis and release of tumor-associated antigens Activation of endosomal TLR-9 in infiltrated APCs Enhancement of secretion of PICs such as IL-6 and TNF-α | [160] | |
| Hydrogel NPs (α-Cyclodextrin-PEG/Intratumoral) | CpG NP | Melanoma |
Modulation of TME toward immune-suppressive condition Enhancement in the number of CTLs and ratio of CD8+ T/Tregs Reduction in the number of MDSC and M2-like TAMs | [134] | |
| Polymeric NPs (AC-CS-PpIX micelle and PBA-PEG-PCL (DOX)b/Intratumoral and IV) | TLR7 agonist, Imiquimod (R837) | Breast cancer and MQ models |
Enhanced anti-tumor immune response Enhanced expression of IL-6, TNF-α, IL-1β, and IFN-γ, and decrease in level of IL-10 expression Higher tumor inhibition rate (85%) and an improved survival rate of treated mice (80%) | [161] | |
| Polymeric NPs (γ-PGA/Intratumoral) | PTX | TLR-7 agonist, Imiquimod | Melanoma, lung cancer, and cervical cancer |
Extreme prevention of tumor growth Enhanced activation and proliferation of the DCs and secretion of PICs and Th1 cytokines Enhancement of the population of DCs and MQs in the tumor-draining lymph node | [103] |
| (Lipophilic prodrugs nanoassemblies/IV) | TLR7 agonist, Imiquimod | Breast cancer |
Effective induction of apoptosis and inhibition of tumor growth and angiogenesis, with no tumor recurrence Stimulation of DCs through collaboration of TAAs with R837 leading to potent tumor-specific immune response | [162] | |
| Biomimetic NPs (HDL nanodiscs/Intratumoral) | DTX | TLR9 agonist, CpG ODN | Colon carcinoma |
Maximum anti-tumor efficacy and minimum off-target side effects Significant improvement in overall survival in combination-treated mice toward mice treated with DTX alone | [163] |