Target Nanoparticles against Pancreatic Cancer: Fewer Side Effects in Therapy
Abstract
:1. Introduction
2. Pancreatic Cancer
2.1. Pancreatic Cancer Biology
- Pancreatic intraepithelial neoplasms (PanIN), which are non-invasive microscopic lesions that occur in small pancreatic ducts (less than 0.5 cm).
- Intraductal papillary mucinous neoplasms (IPMN), precursor lesions of pancreatic cancer.
- Mucinous cystic neoplasms (MCN), which are also considered premalignant lesions of the pancreas and occur more frequently in women [29].
- Adenosquamous carcinoma, which has the worst prognosis.
- Mucinous carcinoma, with a favorable prognosis and is related to the lesion called intraductal papillary mucinous neoplasia.
- Undifferentiated anaplastic carcinoma, which is considered the most aggressive of the subtypes, with an extremely low survival rate due to its atypical cells mixed with osteoclast-like giant cells.
2.2. Clinical Aspects of Pancreatic Cancer
2.3. Current Pancreatic Cancer Treatments
2.4. Surface Protein as Target in Pancreatic Cancer
3. Nanoparticles as a Therapeutic Strategy in Cancer
3.1. Nanoparticles for Drug Delivery
3.2. Nanoparticles as a Vehicle for DNA (Gene Therapy)
3.3. Nanoparticles as a Vehicle for RNAi (Gene Therapy)
3.4. Nanoparticles for Photothermal Therapy
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Nanoparticle | Unique Properties | Medical Use in Cancer | References |
---|---|---|---|
Magnetic nanoparticles (MNPs) | Can be detected and manipulated by remote magnetic fields, can generate heat when exposed to an alternating magnetic field. | Magnetic biosensing, magnetic imaging, and magnetic separation (diagnostics). Drug and gene delivery, and hyperthermia therapy. | [5,16,17] |
Gold nanoparticles (AuNPs) | Surface plasmon resonance, surface multi-functionalization, facile synthesis, stable nature, non-toxic and non-immunogenic nature, high permeability and retention effect, easy penetration and accumulation at tumor, can absorb near-infrared (NIR) light at 650–900 nm and convert it to heat. | Tumor detection by imaging (diagnostics). Treatment of cancer by drug delivery, photothermal and photodynamic therapy. | [5,17,18] |
Polymeric nanoparticles | Biodegradable, increase the circulation time of drugs in the body, can target molecules with minimal side-effects, non-activation of the mononuclear phagocyte system. | Polymeric nanocarrier system for drug delivery in chemotherapy. Cationic charged polymers can carry nucleic acids (gene therapy). Controlled drug delivery. | [19,20] |
Liposomes | Biocompatible, highly flexible, can carry different types of therapeutic molecules, can be tailored to extend blood circulation time, can be targeted. Several liposomes (lipidic nanoparticles) are on the market. | Drug delivery, long-circulating (PEGylated) liposomes, gene therapy, ligand-targeted liposomes, liposomes containing combinations of drugs. Delivery of anti-fungal, antibiotic, anesthetic, and anti-inflammatory drugs. | [21,22] |
Micelles | Self-assembly, condensation and protection of nucleic acids, cell association, gene transfection, low toxicity. | Gene delivery | [23] |
Carbon nanotubes (CNTs) | Can penetrate cell membranes, the sp2 hybridization of all carbons enables their functionalization with almost every biomolecule or compound, allowing them to target cells and deliver drugs under the appropriate environmental stimuli, can absorb near-infrared (NIR) light at 650–900 nm and convert it to heat. | Drug delivery and hyperthermia therapy. | [24] |
Drug | Action Pathway | Common Adverse Side Effects (>30%) | Less Common Adverse Side Effects (<30%) | References |
---|---|---|---|---|
5-FU Capecitabine Gemcitabine | Pirimidin antagonist | Diarrhea, occasional nausea, vomiting, mouth sores, poor appetite, watery eyes, sensitivity to light (photophobia), metallic taste in the mouth during the infusion, anemia. | Skin reactions: dryness, cracking, peeling of the skin, darkening of the skin due to hypersensitization to radiation, skin rash, swelling, redness, pain, peeling of the skin on the palms of the hands and the soles of the feet. Hair thinning, nail discoloration, falling of the nails, hand-and-foot syndrome (palmar-plantar erythrodysesthesia). | [40,41,42] |
Paclitaxel (Abraxane®) | Mitotic block by stabilizing microtubules. | Low blood counts, hair loss, peripheral neuropathy, abnormal ECG, nausea, weakness, fatigue, diarrhea, poor appetite, arthralgias, myalgias, edema, and fever. | Infections, dehydration, constipation, taste changes, skin rash, headache, eye problems, depression, mouth sores, shortness of breath, cough, nose bleeds. | [43,44,45,46,47] |
Cisplatin Oxaliplatin | Chelant | Nausea and vomiting. Nausea can last up to 1 week after treatment. Renal toxicity occurs 10 to 20 days after treatment and is usually reversible. Reduction of the concentration of magnesium, calcium, and potassium. Leukopenia and anemia. | Peripheral neuropathy: despite being rare, a serious side effect of decreased sensation and paresthesia can be observed. Sensory loss, numbness and tingling, and difficulty walking can last at least during therapy. These side effects can get progressively worse with treatment. The neurological effects can be irreversible. High frequency deafness. Ringing in the ears. Lack of appetite, alterations in taste, metallic taste. Increased values in blood tests that measure liver function. Hair loss, fever. Cisplatin can also affect fertility. | [48,49] |
Irinotecan (Onivyde®) | Topoisomerase I inhibitor | Early diarrhea occurs within 24 h of drug administration. It is accompanied by symptoms such as a runny nose, increased salivation, tearing, sweating, erythema, and abdominal cramps. This type of diarrhea can occur during drug administration. Late diarrhea occurs 24 h after drug administration and usually reaches its highest intensity around 11 days after treatment. Dehydration and electrolyte imbalance. Nausea, vomiting, weakness, leukopenia, anemia. | Hair loss, poor appetite, fever, weight loss, constipation, dyspnea, insomnia, cough, headache, dehydration, shaking chills, acne, flatulence, erythema of the face, mouth sores, heartburn, swelling in the feet and ankles. | [50] |
Surface Protein in Pancreatic Cancer 1 | Relevance | References |
---|---|---|
TFRC | Transferrin receptors (TFRC) are over expressed in 93% of the pancreatic cells. In 2019, Wu demonstrated that nanoparticles can be targeted to pancreatic cancer cells using an aptamer that binds with transferrin receptor protein 1 also known as CD71. | [51,52] |
FC | Folate receptor (FR) is a glycosylphosphatidylinositol expressed in more than the 80% of the pancreatic cancer patients. It has a limited expression in healthy cells. | [51,53] |
DR5 | DR5 is significantly higher than stage II, III, and IV tumors than in stage I tumors. DR5 is associated with TRAIL resistance. | [54] |
LOXL2 | Regulates the expression of EMT markers. LOXL2 overexpression correlates with poor prognosis in patients with pancreatic cancer. | [55] |
HGF | Modulate multiple cell functions, including proliferation, motility, migration, and invasion. | [56] |
PD-1/PDL1 | PD-L1 is expressed in PDAC, and its overexpression is associated with a poor prognosis. Previous studies reported divergent tumoral PD-L1 levels, ranging from 12 to 90%. | [57,58,59] |
VEGF | An important factor regulating angiogenesis, VEGF, is over expressed in more than 90% of PDACs and correlates with a worse prognosis. Seo et al. demonstrated that 93% of PDAC were positive for VEGF protein. | [60,61,62] |
HER2 or ERBB2 | HER2 protein expression is associated with decreased survival rate. HER2 is overexpressed in 45% of PDAC. | [63] |
EGRF | EGFR is overexpressed in 40–70% of pancreatic cancers. Overexpression is correlated with metastasis to other organs. | [64,65,66] |
IGF-IR | Overexpression and excessive activation of IGF-IR are associated with malignant transformation, increment of tumor aggressiveness, and protection from apoptosis. IGF-IR targets 70 to 100% of the core metabolic pathways that are often altered in PDAC pathogenesis. | [67,68] |
PSCA | Overexpressed in approximately 60% of pancreatic cancers. | [69] |
CD40 | CD40 agonists tumor growth suppression and extended survival. | [70,71,72] |
GCC | GCC is a transmembrane G protein cell-surface receptor activated by the endogenous hormones guanylin and uroguanylin and bacterial heat-stable enterotoxins that plays a role in regulation of fluid and electrolyte balance. It is highly expressed in colorectal cancer and about 60–70% of pancreatic cancers. It is shown to inhibit the growth-suppressing activity of GCC in pancreatic cancer cell lines and pancreatic-patient-derived xenograft (PDX) models. | [73,74,75] |
CA19-9 | An attractive therapeutic target for PCAD is carbohydrate antigen 19-9 (CA19-9), known as sialyl Lewis A (sLea). It represents a validated biomarker widely used for diagnostic and prognostic in pancreatic cancer. It is a useful predictor of tumor stage and resectability and response to therapy, and is useful for assessing overall survival. A reduction in CA19-9 is an indicator of treatment benefit. | [76,77] |
SLC44A4 | Localized in tumor stroma, fibroblasts, and tumor epithelial cells. This protein has been evaluated as a prognostic and predictive biomarker. | [78] |
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Roacho-Pérez, J.A.; Garza-Treviño, E.N.; Delgado-Gonzalez, P.; G-Buentello, Z.; Delgado-Gallegos, J.L.; Chapa-Gonzalez, C.; Sánchez-Domínguez, M.; Sánchez-Domínguez, C.N.; Islas, J.F. Target Nanoparticles against Pancreatic Cancer: Fewer Side Effects in Therapy. Life 2021, 11, 1187. https://doi.org/10.3390/life11111187
Roacho-Pérez JA, Garza-Treviño EN, Delgado-Gonzalez P, G-Buentello Z, Delgado-Gallegos JL, Chapa-Gonzalez C, Sánchez-Domínguez M, Sánchez-Domínguez CN, Islas JF. Target Nanoparticles against Pancreatic Cancer: Fewer Side Effects in Therapy. Life. 2021; 11(11):1187. https://doi.org/10.3390/life11111187
Chicago/Turabian StyleRoacho-Pérez, Jorge A., Elsa N. Garza-Treviño, Paulina Delgado-Gonzalez, Zuca G-Buentello, Juan Luis Delgado-Gallegos, Christian Chapa-Gonzalez, Margarita Sánchez-Domínguez, Celia N. Sánchez-Domínguez, and Jose Francisco Islas. 2021. "Target Nanoparticles against Pancreatic Cancer: Fewer Side Effects in Therapy" Life 11, no. 11: 1187. https://doi.org/10.3390/life11111187