Nanoplatform-Mediated Autophagy Regulation and Combined Anti-Tumor Therapy for Resistant Tumors

Figures & data

Figure 1 The mechanisms of multi-drug resistance in tumor especially the autophagy mechanism.

Figure 2 The different role of autophagy in tumor drug resistance.

Table 1 The Combination Therapy Co-Delivered by Nanoparticles

Combination Therapy	Drug	Nanomedicine	Tumor
Chemotherapy + Chemotherapy	Doxorubicin+paclitaxel Vincristine+topotecan	Co-NPs^Citation81 LipoViTo^Citation82	Lung cancer Medulloblastoma
Chemotherapy + Cell apoptosis inducer	Doxorubicin+curcumin Paclitaxel+curcumin	DOX+CUR loaded NPs^Citation83 Combination TF-Micelles^Citation84	Chronic myeloid leukemia Ovarian cancer
Chemotherapy + Targeted therapy	Doxorubicin+paclitaxel+trastuzumab	DENCs^Citation85	Breast cancer
Chemotherapy + MDR inhibitor	Doxorubicin+verapamil Docetaxel+chloroquine	CL-R8-LP (DOX + VER)^Citation86 Docetaxel-loaded PEG-b-PLGA micelles^Citation87	Breast cancer Breast cancer
Chemotherapy +Chemokinetic	Doxorubicin+NO	Dox&TNO3^Citation88	Liver cancer
Chemotherapy + Immunotherapy	Doxorubicin+si-PD-L1	Dox-siRNA/TPTN-NPs^Citation89	Breast cancer
Chemotherapy + Gene therapy	Dichloroacetate+p53 plasmid Docetaxel+MMP-9 shRNA	DSPE-PEG-AA/rHDL/DCA-PEI/p53 complexes^Citation90 PAG/DTX-shRNA micelles^Citation91	Lung cancer Breast cancer
Chemotherapy + Photodynamic	Doxorubicin+chlorin e6	HA-Ce6 (DOX)^Citation92	Lung cancer
Chemotherapy + Photothermal	Doxorubicin+gold	GNR@DOX^Citation93	Metastatic breast cancer
Chemotherapy + Magnetothermal	Daunorubicin+Fe3O4	Fe3O4-MNP-DNR-5-BrTet^Citation94	Leukemia
Chemotherapy + Prodrug	Paclitaxel+prodrug	PTX/CBP NPs^Citation95	Lung cancer
Photothermal + Photothermal	Graphene oxide+gold	FA-GO@Au^Citation96	Breast cancer Cervical cancer
Photodynamic + Targeted therapy	BPD+cetuximab Photosensitizer MOF+apatinib	PICAL^Citation97 aMMTm^Citation98	Ovarian cancer Breast cancer
Sonodynamic + Immunotherapy	HMME+R837	HMME/R837@Lip^Citation99	Breast cancer
Prodrug + Prodrug	Cisplatin(IV) conjugate+paclitaxel conjugate	M(PTX/Pt)^Citation100	Ovarian cancer
Prodrug + Photodynamic	Tirapazamine (TPZ) ICG	iNP/IT^Citation101	Breast cancer
Prodrug + Gene therapy	PC-Dox+p53 plasmid CPT-PCB+siPlk1	PC-Dox/p53 nanocomplexes^Citation102 CPT-PCB/siPlk1 lipoplexes^Citation103	Breast cancer Cervical cancer
Immunotherapy + Immunotherapy	a-CTLA-4+a-PD-1 TGF-β+IL-2 NLG919+PD-L1 inhibitor	NICs^Citation104 nLGs^Citation105 NLG919@DEAP-^DPPA-1^Citation106	Glioma Metastatic melanoma Melanoma

Figure 3 Nanotechnology based co-delivery system to deliver different treatment drugs. (A) The model of the co-delivery system; (B) The example of co-delivery system based on nanotechnology.

Notes: (A) Is created with BioRender.com. (B) Is reproduced with permission from Cheng K, Ding Y, Zhao Y, et al. Sequentially Responsive Therapeutic Peptide Assembling Nanoparticles for Dual-Targeted Cancer Immunotherapy. Nano letters. 2018;18(5):3250–3258.¹⁰⁶ Copyright 2018 American Chemical Society.

Figure 4 Co-delivery of autophagy regulators and anti-tumor therapies based on nanotechnology. (A) The model of the co-delivery method; (B) The example of nanotechnology based co-delivery of autophagy inhibitors and anti-tumor therapies.

Notes: (A) Is created with BioRender.com. (B) Is reproduced from Ma Z, Lin K, Tang M, et al. A pH-Driven Small-Molecule Nanotransformer Hijacks Lysosomes and Overcomes Autophagy-Induced Resistance in Cancer. Angew Chem Int Ed Engl. 2022;61(35):e202204567.¹³⁶ © 2022 Wiley-VCH GmbH.

Table 2 The Combination Therapy with Autophagy Regulators Through Different Nanoplatforms

	Nano-Materials	Delivery Drugs	Delivery Method	Tumor
Organic	PLGA	Docetaxel+CQ	PEG-b-PLGA NPs+free CQ	Breast cancer^Citation87
	PLA	Docetaxel+CQ	DTX-H40-PLA NPs+free CQ	Breast cancer^Citation119
	Amphiphilic peptide micelle system	Doxorubicin+si-Beclin1	Co-delivery system (Co-PM NPs)	Prostate cancer^Citation120
	HBPO (OEI600-PBA)10	Doxorubicin+si-Beclin1	Co-delivery system (HBPO (OEI600-PBA)10/DOX/siRNA)	Cervical cancer^Citation121
	FPDP	Doxorubicin+si-Beclin1	Co-delivery system (FPDP/DOX/shBeclin1)	Liver cancer^Citation122
	liposome	Paclitaxel+CQ PpIX+3MA BTZ+siSHARP1 curcumin+niacin	PTXL NPs+CQL NPs Co-delivery system (PpIX/3-MA@Lip NPs) (Lipo-siRNA-BTZ-PEG-cRGD NPs) (Curcumin-Niacin NPs NPs)	Adenocarcinoma^Citation123 Breast Cancer^Citation142 Acute Myeloid Leukemia^Citation157 Liver cancer^Citation167
	DSPE-PEG	Pt(IV)-peptide-bis(pyrene)+Beclin1 siRNA	Co-delivery system (siBec1@PPN NPs)	Lung Cancer^Citation126
	Tumor cell-derived microparticle	PpIX+3MA	Co-delivery system (HAL/3MA@X-MP NPs)	Breast Cancer^Citation128
	perfluorohexane	Pt(IV)+CQ	Co-delivery system (Pt(IV)/CQ/PFH NPs)	Breast Cancer^Citation129
	DMN	IR780+CQ	Co-delivery system (CQ/IR780-Mil NPs)	Melanoma^Citation132
	PBC NPs	PA+BAQ	Co-delivery system (Pheophorbide a (PA)-Bisaminoquinoline (BAQ) Conjugate (PBC NPs))	Oral Cancer^Citation136
	TkPEG	Aggregation induced emission (AIE)+triptolide (TP)	Co-delivery system ((TP+A)@TkPEG NPs)	Breast Cancer^Citation137
	DSPE-PEG-SeSe-COOH	CONs+pTRPM2	Co-delivery system (CONs/pTRPM2 NPs)	Prostatic Cancer^Citation138
	PLGA-PEG	ICG+Daurisoline (DAS) icaritin+doxorubicin	Co-delivery system (PD/I NPs) (PLGA-PEG-AEAA NP NPs)	Breast Cancer^Citation139 Liver Cancer^Citation159
	PEI-HA	PEI+PTX+Mdr1 siRNA	Co-delivery system (PP/siRNA/HA NPs)	Lung Cancer^Citation148
	Alg@CaP	GO+curcumin+Obatoclax	Co-delivery system (GO-Alg@CaP/CO NPs)	Breast Cancer^Citation149
	Macrophage-mimetic Chl (MChl)	Hematoporphyrin+chlorella+CQ	Co-delivery system (MChl-CQ-HP-NP NPs)	Melanoma^Citation151
	Polymers (poly(-caprolactone)) (PCL)	RAPA+9-NC	Co-delivery system (CPAH/CPTAH NPs)	Ovarian cancer^Citation156
	Calcium carbonate	CaCO3+ovalbumin (OVA)	Co-delivery system (HOCN NPs)	Colorectal Cancer^Citation158
	OVA	Bec1+OVA GO+OVA	Co-delivery system (NP-B-OVA NPs) (GO-OVA NPs)	Melanoma^Citation161 Thymoma^Citation162
	PEG-b-PMPC	3-bromopyruvate (3BP) +chlorin e6 (Ce6)	Co-delivery system (CD-Ce6-3BP NPs)	Oral Squamous Cell Carcinoma^Citation163
	polylysine	Lonidamine+ ferrocene+ glucose oxidase	Co-delivery system (FG/T-Nanoprodrug NPs)	Lung cancer^Citation164
	TPGS	TPGS+Sertaconazole (STZ)	Co-delivery system (HA-TPGS-STZ NPs)	Lung cancer^Citation165
	PMBA	Curcumin+Bcl2 siRNA	Co-delivery system (Poly@Cur-FA NPs)	Cervical cancer^Citation166
	HMPB	Curcumin (Cur)+5-fluorouracil (5-Fu) +hollow mesoporous Prussian blue (HMPB)	Co-delivery system (5-Fu/Cur-P@HMPB NPs)	Colorectal cancer^Citation168
	PVP	Photothermal drug+photosensitizer drug+chemokinetic drug	Co-delivery system (PVP-Fe-Cu-Ni-S NPs)	Breast cancer^Citation169
Hybrid	DNA-based hybrid nanosystem	TLR9 agonist+CQP	Co-delivery system (FNC@NF NPs)	Pancreatic Cancer^Citation127
	PEG-BPNS	BPNS+DOX+siClC-3	Co-delivery system (BP-AS@D NPs)	Cervical Cancer^Citation150
Inorganic	FHM	Fe+artemisinin+CQ	Co-delivery system (L-FHM@A-CQ NPs)	Breast Cancer^Citation130
	MOF (ZIF-8)	Fe+MIL88+CQ 2-DG+BAY-876+CQ GOx+CQ	Co-delivery system (CQ-dual MOF NPs) (D/B/CQ@ZIF-8@CS NPs) (CQ@ZIF-GOx NPs)	Lung Cancer^Citation131 Breast Cancer^Citation133 Breast Cancer+Liver Cancer^Citation145
	AuNPs	DOX+CQ Cu2-xSe+Au	Co-delivery system (D&H-AA&C NPs) (Au@Cu2-xSe NPs)	Glioma^Citation134 Glioblastoma^Citation44
	HMSN	SiO2+HCQ	Co-delivery system (HCQ-HMSN NPs)	Colorectal Cancer^Citation135
	Calcium phosphate	GOx+CQ	Ca@GOx NPs+CQ-NPs	Breast Cancer^Citation146
	TeDNB	TeO3^2-+OME	Co-delivery system (TeDNBs-HSA/OME (TeDNBs-HO) NPs)	Breast Cancer^Citation147

Figure 5 Dual regulation of autophagy based on nanotechnology. (A) The model of the dual regulatory function; (B) The example of dual regulation of autophagy in starvation therapy based on nanotechnology.

Notes: (A) Is created with BioRender.com. (B) Is reproduced from Li F, Chen T, Wang F, et al. Enhanced Cancer Starvation Therapy Enabled by an Autophagy Inhibitors-Encapsulated Biomimetic ZIF-8 Nanodrug: Disrupting and Harnessing Dual Pro-Survival Autophagic Responses. ACS Appl Mater Interfaces. 2022;14(19):21860-21871.¹⁷⁰ Copyright 2022 American Chemical Society.

Figure 6 The applications of nanotechnology in combination therapy with autophagy regulator in tumor drug resistance treatment.

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