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 11 Nanocarrier-mediated gene therapy for cancer

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

Gene Therapy Approach	Target Gene	Delivery Method	Transfection Efficiency	Gene Expression Level	Therapeutic Outcome	Description	Novelty	Advantages	Disadvantages	References
Viral vectors	p53	Adenovirus	High	High	Induces apoptosis	Adenovirus is a commonly used vector for gene therapy due to its high transfection efficiency and ability to infect a wide range of cells	The use of adenovirus for p53 gene therapy is a novel approach that has shown promising results in preclinical studies	High transfection efficiency results in high gene expression levels and improved therapeutic outcomes	Adenovirus can induce an immune response, limiting its effectiveness and potential toxicity	[49, 50]
Non-viral vectors	siRNA	Lipid nanoparticles	Moderate	Moderate	Downregulates target gene expression	Lipid nanoparticles are a promising non-viral vector for gene therapy due to their biocompatibility and ability to encapsulate and protect nucleic acids	The use of lipid nanoparticles for siRNA delivery is a relatively new approach that has shown improved transfection efficiency and gene silencing compared to other non-viral vectors	Lower risk of immune response and toxicity compared to viral vectors	Lower transfection efficiency and gene expression levels compared to viral vectors	[49, 50]
CRISPR-Cas9	PD-1	Gold nanoparticles	High	High	Enhances T cell activity	Gold nanoparticles have unique optical and electronic properties that make them promising candidates for gene therapy	The use of gold nanoparticles for CRISPR-Cas9 delivery is a cutting-edge approach that has shown promising results in preclinical studies	High transfection efficiency and gene expression levels	Limited data on long-term safety and potential toxicity	[117]
Electroporation	IL-12	Electric pulses	Moderate	High	Induces immune response	Electroporation is a non-viral method for delivering nucleic acids into cells using brief electric pulses	The use of electroporation for IL-12 gene therapy is a novel approach that has shown promising results in preclinical studies	Non-toxic and non-immunogenic	Requires specialized equipment and expertise	[251]
CRISPR-Cas13a	KRAS	Liposomes	High	Moderate	Downregulates target gene expression	CRISPR-Cas13a is a recently discovered RNA-guided ribonuclease system that can be used for RNA editing	The use of CRISPR-Cas13a for KRAS gene therapy is a cutting-edge approach that has shown promising results in preclinical studies	Specific and efficient targeting of RNA	Limited data on long-term safety and potential off-target effects	[252]
AAV vectors	BDNF	Adeno-associated virus	High	High	Enhances neuronal growth and survival	Adeno-associated virus (AAV) vectors are a type of viral vector that can be used for gene therapy due to their safety and ability to integrate into the host genome	The use of AAV vectors for brain-derived neurotrophic factor (BDNF) gene therapy is a promising approach for treating neurodegenerative diseases	Long-term expression and stability	Limited packaging capacity and potential immune response	[253]
Hybrid viral vectors	HER2	Hybrid viral vectors	High	High	Induces apoptosis	Hybrid viral vectors combine the advantages of different viral vectors to achieve improved transduction efficiency and specificity	The use of hybrid viral vectors for HER2 gene therapy is a promising approach for treating HER2-positive breast cancer	Improved transduction efficiency and specificity compared to single viral vectors	Potential immune response and toxicity	[254]
CRISPR-Cas9	LDLR	Gold nanorods	Moderate	Moderate	Upregulates target gene expression	Gold nanorods are a type of gold nanoparticle that can be used for gene therapy due to their plasmonic properties	The use of gold nanorods for CRISPR-Cas9-mediated LDLR gene therapy is a novel approach that has shown promising results in preclinical studies	Non-toxic and biocompatible	Limited data on long-term safety and efficacy	[117]
Non-viral vectors	BRCA1	Polymeric nanoparticles	High	High	Induces DNA repair	Polymeric nanoparticles are a type of non-viral vector that can be used for gene therapy due to their versatility and biocompatibility	The use of polymeric nanoparticles for BRCA1 gene therapy is a promising approach for treating breast cancer	High transfection efficiency and biocompatibility	Limited packaging capacity and potential toxicity	[49, 50]
In vivo electroporation	IL-10	In vivo electroporation	High	High	Suppresses inflammation	In vivo electroporation is a non-viral method for delivering nucleic acids into cells in vivo using electric pulses	The use of in vivo electroporation for IL-10 gene therapy is a promising approach for treating inflammatory diseases	Non-toxic and non-immunogenic	Limited data on long-term safety and potential toxicity	[255]
CRISPR-Cas12a	EGFR	Lipid nanoparticles	High	Moderate	Downregulates target gene expression	CRISPR-Cas12a is a recently discovered RNA-guided endonuclease system that can be used for gene editing	The use of CRISPR-Cas12a for EGFR gene therapy is a novel approach that has shown promising results in preclinical studies	Specific and efficient targeting of DNA	Limited data on long-term safety and potential off-target effects	[256]
mRNA-based vaccines	SARS-CoV-2 spike protein	Lipid nanoparticles	High	High	Induces immune response	mRNA-based vaccines are a novel approach to gene therapy that use messenger RNA (mRNA) to encode a protein of interest and induce an immune response	The use of mRNA-based vaccines for the SARS-CoV-2 spike protein is a cutting-edge approach for preventing COVID-19	Rapid and scalable production	Potential immune response and toxicity	[257]
CRISPR-Cas9	HPRT	Zinc-finger nucleases	Moderate	Moderate	Gene correction	Zinc-finger nucleases (ZFNs) are a type of engineered DNA-cutting enzyme that can be used for gene editing	The use of ZFNs for HPRT gene therapy is a promising approach for treating genetic disorders	Specific and efficient targeting of DNA	Limited data on long-term safety and potential off-target effects	[117, 258]
Viral vectors	CFTR	Lentivirus	High	High	Induces gene expression	Lentivirus is a type of retrovirus that can be used as a vector for gene therapy	The use of lentivirus for CFTR gene therapy is a promising approach for treating cystic fibrosis	High transduction efficiency and stable gene expression	Potential immune response and toxicity	[259]
Non-viral vectors	VEGF	Dendrimers	Moderate	Moderate	Enhances angiogenesis	Dendrimers are a type of branched polymer that can be used as a non-viral vector for gene therapy	The use of dendrimers for VEGF gene therapy is a novel approach that has shown promising results in preclinical studies	Highly customizable and biocompatible	Limited transfection efficiency and potential toxicity	[260]
CRISPR-Cas9	DMD	AAV vectors	High	High	Gene correction	Adeno-associated virus (AAV) vectors are a type of viral vector that can be used for gene therapy	The use of AAV vectors for DMD gene therapy is a promising approach for treating Duchenne muscular dystrophy	Long-term gene expression and safety	Limited packaging capacity and potential immune response	[117]
mRNA-based therapies	OCT4	mRNA electroporation	High	High	Induces cell reprogramming	mRNA-based therapies are a novel approach to gene therapy that use messenger RNA (mRNA) to encode a protein of interest	The use of mRNA electroporation for OCT4 gene therapy is a cutting-edge approach for inducing cell reprogramming	Rapid and customizable production	Potential immune response and toxicity	[261]
Non-viral vectors	MDR1	Nanoparticles	Moderate	Moderate	Downregulates target gene expression	Nanoparticles are a type of non-viral vector that can be used for gene therapy due to their size and biocompatibility	The use of nanoparticles for MDR1 gene therapy is a promising approach for overcoming multidrug resistance in cancer	Non-toxic and biocompatible	Limited transfection efficiency and gene expression levels	[49, 50]
CRISPR-Cas9	HBB	Lipid nanoparticles	High	High	Gene correction	Lipid nanoparticles are a type of non-viral vector that can be used for gene therapy due to their biocompatibility and ease of production	The use of lipid nanoparticles for HBB gene therapy is a promising approach for treating sickle cell disease	Non-immunogenic and scalable production	Limited transfection efficiency and gene expression levels	[117]
Gene silencing	BCL-2	Aptamers	High	Moderate	Downregulates target gene expression	Aptamers are a type of synthetic nucleic acid that can be used as a gene silencing agent	The use of aptamers for BCL-2 gene therapy is a novel approach that has shown promising results in preclinical studies	Specific and efficient targeting of RNA	Limited in vivo stability and potential immunogenicity	[262]
Non-viral vectors	FGF2	Cationic liposomes	Moderate	Moderate	Enhances angiogenesis	Cationic liposomes are a type of non-viral vector that can be used for gene therapy due to their ability to interact with cell membranes	The use of cationic liposomes for FGF2 gene therapy is a promising approach for promoting tissue regeneration	Low toxicity and customizable	Limited transfection efficiency and stability	[49, 50, 263]
CRISPR-Cas9	CFTR	CRISPR-Cas9 ribonucleoprotein	High	High	Gene correction	CRISPR-Cas9 ribonucleoprotein is a recently developed gene editing technology that uses RNA-guided endonucleases	The use of CRISPR-Cas9 ribonucleoprotein for CFTR gene therapy is a promising approach for treating cystic fibrosis	High specificity and efficiency	Potential off-target effects and immune response	[117, 264]
RNA interference	KRAS	Gold nanoparticles	Moderate	Moderate	Downregulates target gene expression	Gold nanoparticles are a type of nanoparticle that can be used for gene therapy due to their unique optical and electronic properties	The use of gold nanoparticles for KRAS gene therapy is a novel approach that has shown promising results in preclinical studies	High biocompatibility and stability	Limited transfection efficiency and potential toxicity	[194, 195]
Viral vectors	APOE	Adenovirus	High	High	Upregulates target gene expression	Adenovirus is a type of viral vector that can be used for gene therapy due to its high transduction efficiency	The use of adenovirus for APOE gene therapy is a promising approach for treating Alzheimer's disease	High transduction efficiency and long-term gene expression	Potential immune response and toxicity	[265]
RNA interference	TP53	Nanoparticles	High	High	Downregulates target gene expression	Nanoparticles are a type of non-viral vector that can be used for gene therapy due to their size and biocompatibility	The use of nanoparticles for TP53 gene therapy is a promising approach for treating various cancers	Non-toxic and biocompatible	Limited transfection efficiency and gene expression levels	[193]
Gene editing	F9	CRISPR-Cas9	High	High	Gene correction	CRISPR-Cas9 is a gene editing technology that uses RNA-guided endonucleases to modify DNA	The use of CRISPR-Cas9 for F9 gene therapy is a promising approach for treating hemophilia B	High specificity and efficiency	Potential off-target effects and immune response	[266]
mRNA-based therapies	FLT3L	mRNA electroporation	High	High	Induces immune response	mRNA-based therapies are a novel approach to gene therapy that use messenger RNA (mRNA) to encode a protein of interest	The use of mRNA electroporation for FLT3L gene therapy is a cutting-edge approach for enhancing immune response	Rapid and customizable production	Potential immune response and toxicity	[194, 195]

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