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Table 2 NP materials in targeted cancer therapy with potential in GI treatment

From: Nano drug delivery systems in upper gastrointestinal cancer therapy

NP Type

Material

Advantages

Disadvantage

FDA approval/clinical status

Refs.

Polymer

PLGA

Enhanced drug solubility,improved accumulation at tumor site, completely biodegradable, non-toxic clearance, suitable for surface modifications, dual functionality when conjugated with chitosan or gold, use in photothermal therapy, vaccine and gene delivery, easy and proven processing

More toxicity studies and clinical evaluation needed, possible immunogenic properties

Approved for drug delivery. Clinical trial: PEG-PLGA docetaxel, paclitaxel PEG-PLGA, paclitaxel oncoGel

[174, 175]

Chitosan

Antimicrobial properties, solubility, stability and biocompatability, coating for other NPs, cationic and mucoadhesive characteristics—ideal for oral delivery, permeation enhancement, pH responsive, excellent gene and cancer vaccine delivery vector

Low solubility in non-acidic pH, lack of comprehensive toxicity profile, deacetylation degree determines physio-chemical behaviour, crosslinking might prevent degradation

Approved as safe. Animal studies on DOX-chitosan. Clinical studies (mainly lung and breast cancer): chitosan NPs loaded with curcumin, cisplatin or ascorbate

[77, 176]

Collagen

Conjugation with metal NPs, high biocompatibility, suitable for inhalation, controlled release

Delivery of collagenase desireable in cancer—not possible with collagen, difficult particle fabrication

Research: silver NP stabilized with collagen

[177, 178]

Alginate

Mucoadhesive, pH sensitive, oral delivery, suitable for micelles, stabilizer for metal NPs

Unknown toxicity, need stabilizers

Preclinical studies: magnetic chitosan/alginate- curcumin NP, exemestane-ALG-NPs, paclitaxel-loaded ALG-NP

[155, 156]

Cellulose

pH triggered release, completely biodegradable, oral administration, increase drug solubility

Difficult fabrication, aggregation due to hydrophylic nature, no release in acidic pH (GC), insufficient knowledge about interaction with cells and tissues

Approved: carboxymethyl cellulose. Clinical Trial: eethylcellulose + cetuximab

[76, 179, 180]

Metal

Se

Antioxidant, anti-inflammatory properties, anticancer activity, dual delivery of therapeutics like siRNA + cisplatin, curcumin SeNPs

Dual role in cancerogenesis and drug delivery—might also produce radicals, possible epigenetical modifications

Only in vitro cell studies

[167, 181, 182]

Au

High surface to volume ratio, stable, ideal plasmon resonance for therapeutic applications like photothermal and photodynamic therapy, good biosafety profile, high permeability, scalable

Limitations regarding bioavailability of drugs, possible cytotoxicity depending on shape and size, changes in gene expression

Approval: DOX-AuNP, clinical trial: oxaliplatin-platinium-AuNP

[183]

Superpara-magnetic \(Fe_3O_4\)

Magnetic nanocomposites as contrast agents for MRI imaging, drug release control, hyperthermia agents, enhancement of radiation therapy

Possible immunotoxicity, toxicity due to formulation of hydroxyl radicals

Approval only for ferumoxytol (chronic kidney disease), to date no FDA approval for cancer imaging and treatment, late stage clinical trials for Nanotherm(R) ablation therapy (currently approved in Europe for Glioblastoma)

[33, 34, 184,185,186]

Inorganic

\(SiO_2\) carriers

Large specific surface area and pore volume for drug loading, controlled release kinetics, targeted delivery via surface modifications, endocytotic behavior, good biocompatibility, suitable for oral administration and bioimaging

Insufficient information about clearance time, immunogenicity and accumulation in tissue, lack of toxicity data

Silica NP with C dots approved for stage I clinical trial, in vitro cell studies for Paclitaxel-loaded SeNPs

[36, 37]

Carbon NPs/nanotubes graphene oxide, nanodiamonds

Resist harsh acidic environment, biocompatible, able to overcome GI barriers, thermal conductivity, scalable

Poor bioavailability and solubility, intrinsic toxicity

HeLa cell studies for Cisplatin delivery

[163, 187, 188]

Lipid

Liposome

Excellent solubility, high bioavailability and biocompatibility, biodegradable, drug protection, thermosensitive, multidrug loading

Rapid clearance without stabilizing conjugates, possible toxicity, poor knowledge about internalization processes,

Approval: nanoliposomal Irinotecan, PEG-liposomal doxorubicin. Clinical Trial: paclitaxel liposome, liposomal doxorubicin, cisplatin, oxaliplatin, aroplatin and GEM

[122, 189,190,191]

PEG-lipid micelles

Improved stability and drug solubility, enhanced permeability and retention due to small size (\(<100\,\text {nm}\)), cell internalization, programmable thermo-responsiveness, increased effectiveness against resistant cancer, multidrug loading

Antibody response against PEG component, lack of consistent behaviour regarding biodistribution and absorption

Approved: the polymer PEG. Clinical trials: Paclitaxel micelles in combination with cisplatin, docetaxel-polymeric micelles and oxaliplatin, gemcitabine with micellar cisplatin (NC-6004), curcumin-loaded micelles

[93, 192,193,194]

Protein-Based

Pyruvate dehydrogenase E2

Biomimetic platforms for mimicking, viruses, dendritic cell activation, and cross-presentation, cancer vaccine platform

B16 melanoma murine model

Only delay in tumor development, no clinical studies

[195]

Albumin

High solubility of chemodrugs like paclitaxel, various binding capacities, excellent safety profile, biodegradable

Approved: Nab-Paclitaxel

Oral delivery not possible due to degradation in GI system, binding of active agents could lead to protein conformational changes

[196]