Cell-Based Drug Delivery Systems with Innate Homing Capability as a Novel Nanocarrier Platform

Figures & data

Table 1 Applications of Cell-Based Drug Delivery Systems

Drug Loading Method		Cells	Drugs	Disease or Target	Ref.
Encapsula-tion	Phagocytosis	Monocytes, macro-phages	(IgG/albumin-coated), SPIO NPs	Lymphoid tissues	[167]
		Platelets	Antibiotics	Bacterial cells	[168]
	Electroporation	Macrophages	Liposomal DOX	Lung cancer	[169]
		RBCs	Alcohol and aldehyde dehydrogenases	RES-related organs	[170]
	Hypotonic swelling	RBCs	Thymidine phosphorylase	Mitochondrial neuro-gastrointestinal encephalomyo-pathy	[171]
Surface attachment	Noncovalent coupling	RBCs	Anti-ICAM-1 antibody	Lung	[172]
	Covalent conjugation	T cells	NSC-87877-loaded NP	Prostate cancer	[173]
		RBCs	Hyperbranched polyglycerol	RES-related organs	[174]
	Ligand-receptor binding	MSCs	P-selectin	Vascular injury	[175]
		MSCs	Silica nanorattle-DOX NPs	U251 glioma tumor cells	[150]
		Platelets	DOX, CD22 monoclonal antibody	B-cell lymphoma	[176]
	Biotinylation	MSCs	Curcumin-loaded chitosan NPs	Lung metastases	[177]
		T cells	Polystyrene NPs/microparticles	Central nervous system	[178]
		MSCs	DOX-polymer conjugates	Lung metastases	[154]

Abbreviations: DOX, doxorubicin; CD, cluster of differentiation; ICAMs, intercellular adhesion molecules; IgG, immunoglobulin G, MSCs, mesenchymal stem cells; NPs, nanoparticles; NSC, neural stem cell; RBCs, red blood cells; RES, reticuloendothelial system; SPIO, superparamagnetic iron-oxide.

Figure 1 Scheme of living cell-based drug delivery systems.

Figure 2 Mechanism of neutrophil tumor homing.

Figure 3 Mechanisms of hypoxic tumor microenvironment.

Figure 4 Engineering strategies to load drug therapeutics inside of/onto cells. (A) Endocytosis, (B) Electroporation, (C) Hypotonic swelling, (D) Covalent conjugation, (E) Ligand-receptor binding, and (F). Biotinylation.

Table 2 Clinical Trials of Cell-Based Delivery Systems

Cell Type	Therapeutics	Application	ClinicalTrials.Gov Identifier/Ref
RBCs	L-Asparaginase	Leukemia	NCT01518517, NCT00723346, NCT01523782
		Pancreatic cancer	NCT03665441, NCT02195180
		Breast cancer	NCT03674242
	Pembrolizumab	Solid tumor, AML	NCT04372706
	Dex-21-P	Ataxia telangiectasia	NCT01255358, NCT02770807
		COPD	[^Citation179]
Monocytes	CMV pp65-LAMP mRNA	GBM	NCT04741984
Macrophages	Anti-HER2 CAR-M	HER2-positive adenocarcinoma	NCT04660929
T cells	CD19 CAR-T cell	B-cell precursor acute lymphoblasticleukemia	STN: 125646
	Fourth generation CAR-T cells	Nectin4-positive Advanced Malignant Solid Tumor	NCT03932565, NCT04833504
MSCs	PROCHYMAL	Crohn’s disease	NCT00482092
	Cx601		NCT03279081
NSCs	5-FU	GBM	NCT01172964, NCT02015819
	SN-38	GBM	NCT02192359

Abbreviations: RBCs, red blood cells; MSCs, mesenchymal stem cells; NSCs, neural stem cells; Dex-21-P, dexamethasone 21-phosphate; COPD, chronic obstructive pulmonary disease; CMV, cytomegalovirus; LAMP, lysosomal-associated membrane protein; mRNA, messenger ribonucleic acid; GBM, glioblastoma; HER2, human epidermal growth factor receptor 2; CAR, chimeric antigen receptor; M, macrophage; CD, cluster of differentiation; 5-FU, 5-fluorouracil.

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