Progressing nanotechnology to improve targeted cancer treatment: overcoming hurdles in its clinical implementation

Chehelgerdi, Mohammad; Chehelgerdi, Matin; Allela, Omer Qutaiba B.; Pecho, Renzon Daniel Cosme; Jayasankar, Narayanan; Rao, Devendra Pratap; Thamaraikani, Tamilanban; Vasanthan, Manimaran; Viktor, Patrik; Lakshmaiya, Natrayan; Saadh, Mohamed J.; Amajd, Ayesha; Abo-Zaid, Mabrouk A.; Castillo-Acobo, Roxana Yolanda; Ismail, Ahmed H.; Amin, Ali H.; Akhavan-Sigari, Reza

doi:10.1186/s12943-023-01865-0

Molecular Cancer

Table 2 Comparison of cancer targeting agents

From: Progressing nanotechnology to improve targeted cancer treatment: overcoming hurdles in its clinical implementation

Targeting Agent Type	Target Antigen	Affinity	Specificity	Binding Site	Targeted Therapy Type	Description	Novelty	Advantages	References
Monoclonal antibodies (mAbs)	CD20	High	Specific	Epitope on B-cell surface	Immunotherapy	First-line treatment for non-Hodgkin lymphoma and chronic lymphocytic leukemia	Highly specific to target antigen	Target other healthy cells with similar antigen, Costly production	[48]
Antibody–drug conjugates (ADCs)	HER2	High	Specific	Epitope on HER2-positive cancer cells	Chemotherapy	Targeted delivery of cytotoxic agents to HER2-positive cancer cells	Reduced side effects compared to traditional chemotherapy	Limited therapeutic window, Risk of resistance development	[49, 50]
Bispecific T cell engagers (BiTEs)	CD19 and CD3	High	Specific	Epitopes on B-cell and T-cell surfaces	Immunotherapy	Redirect T cells to attack CD19-positive B cells	High potency, Lower toxicity compared to CAR T cell therapy	Limited to CD19-positive cancers, Potential for cytokine release syndrome	[51]
Peptide ligands	VEGF receptor	Moderate	Specific	Ligand-binding site on VEGF receptor	Anti-angiogenic therapy	Inhibit angiogenesis by blocking VEGF receptor signaling	Low immunogenicity, Easier to produce than mAbs	Short half-life, Rapid clearance	[52]
Aptamers	PDGF	High	Specific	Binding site on PDGF	Anti-angiogenic therapy	Inhibit PDGF signaling to block angiogenesis	High binding affinity, Low immunogenicity, Easier to produce than mAbs	Short half-life, Limited in vivo stability	[44]
Nanobodies	EGFR	High	Specific	Epitope on EGFR	Immunotherapy	Target EGFR-positive cancer cells for imaging and therapy	Small size, High specificity, High in vivo stability	Limited penetration of solid tumors, Limited capacity for multivalent binding	[53]
CAR T cells	CD19	High	Specific	Epitope on B-cell surface	Immunotherapy	Genetically engineered T cells that express a chimeric antigen receptor (CAR) for CD19	High efficacy, Durable response, Curative potential for some hematological malignancies	Risk of severe toxicity including cytokine release syndrome and neurotoxicity, High cost	[54]
Radioimmunotherapy (RIT)	CD20	High	Specific	Epitope on B-cell surface	Radiation therapy	Combine the specificity of mAbs with the therapeutic potential of ionizing radiation	Selectively target and destroy cancer cells, Potential for long-term response	Limited to CD20-positive cancers, Risk of toxicity to normal tissue, Complex production process	[48, 54]
Small molecule inhibitors	BCR-ABL	High	Specific	Active site of BCR-ABL kinase	Targeted therapy	Inhibit the activity of cancer-promoting proteins	Oral administration, High selectivity, Overcome resistance to traditional chemotherapy	Limited to cancers driven by specific mutations, Development of resistance	[49, 50]
Viral vectors	HER2	High	Specific	Epitope on HER2-positive cancer cells	Gene therapy	Deliver therapeutic genes to HER2-positive cancer cells	High specificity and selectivity, Potential for long-term response	Limited to HER2-positive cancers, Potential for toxicity and immune response	[49, 50]
Peptide nucleic acids (PNAs)	KRAS	High	Specific	Target site on KRAS mRNA	Gene therapy	Inhibit the expression of cancer-promoting genes	High specificity, Stable in vivo, Overcome resistance to traditional chemotherapy	Limited to cancers driven by specific mutations, Development of resistance	[55]
Aptamer-drug conjugates (ApDCs)	PSMA	High	Specific	Binding site on PSMA	Chemotherapy	Targeted delivery of cytotoxic agents to PSMA-positive cancer cells	Reduced side effects compared to traditional chemotherapy, Easier to produce than mAbs	Limited therapeutic window, Risk of resistance development	[44]
Peptide vaccines	MUC1	Moderate	Specific	Epitope on MUC1-positive cancer cells	Immunotherapy	Activate the immune system to recognize and attack cancer cells	Induce long-lasting immune responses, Low toxicity	Limited to MUC1-positive cancers, Limited efficacy in solid tumors	[56]
Liposomes	Doxorubicin	Low	Non-specific	Passive targeting to tumors through the enhanced permeability and retention (EPR) effect	Chemotherapy	Deliver drugs to tumors with reduced side effects on healthy tissues	Easier to produce than mAbs, Versatile drug delivery system	Limited selectivity, Variable EPR effect in different cancers	[57]
Gold nanoparticles	EGFR	Moderate	Specific	Epitope on EGFR	Photothermal therapy	Absorb light to generate heat and destroy cancer cells	High biocompatibility, Versatile drug delivery system	Limited penetration of solid tumors, Limited efficacy in deep tissues	[58]
Magnetic nanoparticles	CD44	Low	Non-specific	Magnetic targeting to tumors with external magnetic fields	Chemotherapy	Deliver drugs to tumors with reduced side effects on healthy tissues	Easier to produce than mAbs, Minimal systemic exposure	Limited selectivity, Limited efficacy in deep tissues	[59]
RNA interference (RNAi)	Survivin	High	Specific	Target site on survivin mRNA	Gene therapy	Inhibit the expression of cancer-promoting genes	High specificity, Overcome resistance to traditional chemotherapy	Limited to cancers	[60]
Aptamer-conjugated nanoparticles	Nucleolin	High	Specific	Binding site on nucleolin	Chemotherapy	Targeted delivery of drugs to nucleolin-positive cancer cells	High specificity, Reduced side effects compared to traditional chemotherapy, Easier to produce than mAbs	Limited to nucleolin-positive cancers, Limited in vivo stability	[44]
Antibody-nanoparticle conjugates	CD20	High	Specific	Epitope on B-cell surface	Immunotherapy	Targeted delivery of nanoparticles to CD20-positive cancer cells for imaging and therapy	Increased tumor penetration and retention, High selectivity	Limited to CD20-positive cancers, Risk of immunogenicity	[61]
Tumor-penetrating peptides	iRGD	Moderate	Specific	Binding site on integrins and neuropilin-1	Chemotherapy	Enhance the penetration and accumulation of drugs in tumors	High specificity, Overcome barriers to drug delivery in solid tumors	Limited efficacy in deep tissues, Potential for off-target effects	[43]
Nanobody-drug conjugates	EGFR	High	Specific	Epitope on EGFR	Chemotherapy	Targeted delivery of cytotoxic agents to EGFR-positive cancer cells	Small size, High specificity, Reduced side effects compared to traditional chemotherapy	Limited to EGFR-positive cancers, Limited capacity for multivalent binding	[44]
Dual-targeting antibodies	CD3 and CD20	High	Specific	Epitopes on B-cell and T-cell surfaces	Immunotherapy	Redirect T cells to attack CD20-positive B cells	Increased efficacy, Overcome resistance to monoclonal antibodies	Limited to CD20-positive cancers, Potential for cytokine release syndrome	[61]
Protein cages	Ferritin	Low	Non-specific	Passive targeting to tumors through the EPR effect	Drug delivery	Deliver drugs to tumors with reduced side effects on healthy tissues	Easier to produce than mAbs, Biocompatible	Limited selectivity, Variable EPR effect in different cancers	[28]
Aptamer-siRNA conjugates	VEGF	High	Specific	Binding site on VEGF	Gene therapy	Inhibit VEGF expression to block angiogenesis	High specificity, Overcome delivery challenges	Limited to VEGF-driven cancers, Variable in vivo stability	[44]
Therapeutic antibodies	CTLA-4	High	Specific	Epitope on CTLA-4	Immunotherapy	Block inhibitory signals to activate T cells against cancer cells	High specificity, Durable response, Synergistic with PD-1 blockade	Risk of toxicity, Limited efficacy in solid tumors	[61]
Bifunctional fusion proteins	IL-2 and CD25	High	Specific	Epitopes on T-cell and cancer cell surfaces	Immunotherapy	Stimulate T-cell proliferation and activation against cancer cells	Increased efficacy, Reduced toxicity compared to systemic IL-2	Limited to IL-2-responsive cancers, Limited efficacy in solid tumors	[62]

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