disadvantages of nanotechnology in cancer treatment

Du et al., Tailor-made dual pH-sensitive polymerdoxorubicin nanoparticles for efficient anticancer drug delivery. Chan, Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells. Bethesda, MD 20894, Web Policies Nat. 46, 11381148 (2018), H. Banu et al., Gold and silver nanoparticles biomimetically synthesized using date palm pollen extract-induce apoptosis and regulate p53 and Bcl-2 expression in human breast adenocarcinoma cells. By using immunofluorescence labeling of an anti-Ki67 antibody, the Ki67-positive cells in tumor sections after two tail vein injections of 20mg/kg iron dose of IGF1-IONPs are measured. Control. 9, 789 (2003), P.N. Therefore, only a few numbers of nano-drugs available in market for the treatment of cancer. Moreover, for nanomaterials that do extravasate by crossing the vasculature, deeper penetration to tumor site is impeded by the interstitial tumor matrix. Therefore, synthesis and characterization of the nanomaterials for drug delivery need to be carefully performed to avoid the potential unwanted toxicity of nanocarriers to healthy cells [23]. Active targeting approach has been exploited to increase internalization of nanoparticles by the target cells and improve the drug delivery efficacy. 83, 2835 (2016), Y. Zhao et al., Iron oxide nanoparticles-based vaccine delivery for cancer treatment. 41(7), 25392544 (2012), R. Weissleder et al., Cell-specific targeting of nanoparticles by multivalent attachment of small molecules. Liu et al., developed graphene oxide modified with chitosan followed by conjugation with hyaluronic acid and an anti-cancer drug SNX-2112. 13, 34673480 (2018), J. Guo et al., Aptamer-functionalized PEGPLGA nanoparticles for enhanced anti-glioma drug delivery. Typically not drugs themselves, nanoparticles have the potential to deliver traditional cancer drugs to tumors with fewer side effects, or to enable non-traditional drugs (e.g., proteins or nucleic acids) to be targeted to . Colloids Surf. A recent FDA-approved nano-formulation comprising of liposomal entrapped cytarabinedaunorubicin combination (CPX-351 Vyxeos) has shown 9.6months of overall survival compared with 6.0months of survival for the free form of the drug in patients with newly diagnosed high-risk acute myeloid leukemia [35]. Ligand density on the nanoparticles dictates the strength of avidity towards the substrate, so approaches used to conjugate ligands on the surface of nanoparticles are critical aspects of the targeted systems. eCollection 2023. Nanoparticles in precision medicine for ovarian cancer: From chemotherapy to immunotherapy. 30(10), 25122522 (2013), J. Wu et al., Robust, responsive, and targeted PLGA anticancer nanomedicines by combination of reductively cleavable surfactant and covalent hyaluronic acid coating. Similarly, in an in vivo environment, many smaller proteins and intrinsic biomolecules bind non-specifically on the surface of nanoparticles, commonly known as Vromans effect [58], leading to changed identity of the whole nanosystem. 16(4), 12731304 (2017), Y. Chi et al., Redox-sensitive and hyaluronic acid functionalized liposomes for cytoplasmic drug delivery to osteosarcoma in animal models. Discusses the limitations of target therapy for some cancer patients. Rep. 8(1), 2907 (2018), S. Patra et al., Green synthesis, characterization of gold and silver nanoparticles and their potential application for cancer therapeutics. The site is secure. Res. Chupin, V.P. J. Nanomed. An understanding of nano-bio interfacial interactions and targeting of nanoparticles to the tumor cells is essential for cancer therapy and management. Introduction. Endoplasmic retention is only one of the mechanisms describing tumor biology. These particles can selectively target human osteosarcoma cells and are capable of pH-responsive antitumor drug delivery. Nanotechnology for Cancer Treatment and Management - WebMD The size of the nanomaterials also influences the uptake of the drug by the cells and interactions with specific tissues for therapeutic purposes. Mater. Radiotherapy and chemotherapy are known for significant adverse effects [2], with most methods targeting non-specifically any rapidly dividing cells irrespective of whether they are tumorous or not. et al. Sci. J. Mater. Oncol. Doxorubicin-loaded lactoferrin-PLS displayed stronger inhibitory effects in ASGPR-positive HCC cells than with unmodified PEGylated liposomes. Sahoo, Evaluation of curcumin loaded chitosan/PEG blended PLGA nanoparticles for effective treatment of pancreatic cancer. In vitro and in vivo effects of IGF1-IONPs (insulin-like growth factor 1-iron oxide nanoparticles) and IGF1-IONPs-doxorubicin on cell proliferation and viability. 13, 15051524 (2018), S. Malekmohammadi et al., Immobilization of gold nanoparticles on folate-conjugated dendritic mesoporous silica-coated reduced graphene oxide nanosheets: a new nanoplatform for curcumin pH-controlled and targeted delivery. 1. 12, 67596769 (2017), N. Karki et al., Functionalized graphene oxides for drug loading, release and delivery of poorly water soluble anticancer drug: a comparative study. B Biointerfaces 125, 6572 (2015), Y. Xia et al., pH sensitive liposomes delivering tariquidar and doxorubicin to overcome multidrug resistance of resistant ovarian cancer cells. Theranostics 4(8), 834844 (2014), M. Li et al., Enhanced synergism of thermo-chemotherapy for liver cancer with magnetothermally responsive nanocarriers. 1. Recently, PLGA [poly(lactic-co-glycolic acid)] based nanomaterials have been developed, demonstrating that suitable surface coating of the nanomaterials provides extended circulation time. With current advances in molecular biology and enzyme engineering, there is no limitation to using chemistry methods for surface modification or functionalization of nanoparticles for specificity. Lee, C.-W. Cho, Mechanisms of drug release from advanced drug formulations such as polymeric-based drug-delivery systems and lipid nanoparticles. A recent investigation reported that single walled carbon nanotubes were toxic, and induced death of the organs at higher dosages, whereas multi-walled carbon nanotubes in lower dosages could effectively deliver drug for targeted therapy of abnormal cells in breast cancer [205]. Nanomedicine 10(8), 12331246 (2015), Y. Zhang et al., Polymer-coated hollow mesoporous silica nanoparticles for triple-responsive drug delivery. These are responsive to pH, temperature, enzyme, light, the concentration of glutathione [283]. Adv. Chem. Bogart et al., Nanoparticles for imaging, sensing, and therapeutic intervention (ACS Publications, Washington DC, 2014), Book Nanotechnology: A Revolution in Cancer Diagnosis - PMC Liu et al. J. Chem. J. From the above discussion, it is evident that dendrimers are nanoplatforms which can be tuned for therapeutic applications, and show great promise in the treatment of various cancers. In addition to all the above, a significant setback in nanomedicine commercialization is the clinical translation due to the lack of in-depth understanding of nano-bio interfacial interactions. Significant properties of any nanomaterial used in biomedical delivery are its biocompatibility and biodegradability [228], with the discharged carrier degraded into nontoxic components and cleared through the circulation. The gaps between the endothelial cells in the tumorvasculature can range from 200 to 2000nm depending on the tumor type, localization, and environment. 2015 Jun;93:52-79. doi: 10.1016/j.ejpb.2015.03.018. 8(3), 602616 (2018), M. Wei et al., Lactoferrin-modified PEGylated liposomes loaded with doxorubicin for targeting delivery to hepatocellular carcinoma. ACS Nano 1(1), 5056 (2007), R.P. Nanotechnology is often touted as one of the most promising drug delivery innovations in today's fight against cancer. These smart nanosystems trigger the release of the drug trapped in the pores to the target sites in the presence of either endogenous or exogenous stimuli, with control on the administered dose. Recent approaches have explored concomitantly targeting multiple surface receptors with single nanoparticle systems conjugated with multiple ligands [53]. Schematic illustration representing various challenges involved in the delivery of cancer nanotherapeutics. There are different classes of liposomes used as drug delivery platforms for enhancing the efficacy of cancer therapeutics [232]. Chem. An official website of the United States government. In the study, three different targeted nanoparticles and one non-targeted nanoparticle were used to study the uptake and distribution of iron oxide nanoparticles in the PANC02 mouse pancreatic cancer cell line. Better diagnostics. 519(1), 352364 (2017), Y. Zhao et al., Methotrexate nanoparticles prepared with codendrimer from polyamidoamine (PAMAM) and oligoethylene glycols (OEG) dendrons: antitumor efficacy in vitro and in vivo. Nanotechnol. J. Nanomed. 2023 Feb 26;13(5):876. doi: 10.3390/nano13050876. Disadvantages Nanotechnology offers many potential advantages, however, there are also potential disadvantages of nanotechnology, including: Health risks: There is some concern that exposure to nanoparticles could be harmful to human health, as they can easily penetrate cells and tissues. Chauhan, R.K. Jain, Strategies for advancing cancer nanomedicine. Kim et al., Entrapment of hydrophobic drugs in nanoparticle monolayers with efficient release into cancer cells. Artif. This phenomenon can be further exploited for potential therapeutic purposes, employing nanoparticles as drug or gene delivery carriers. Additionally, while it is evident that nanoparticles permeability should normally be at higher rates in hypoxic core of tumor area rather than the periphery, few studies contrast this observation [37]. Google Scholar, J.D. Soc. Likewise, intracellular drug delivery can be enhanced by utilizing carbon nanotube-based phototherapies. J. The cytotoxicity of doxorubicin-loaded mesoporous silica nanomaterials toward cancer cells overexpressing CD44 receptor was enhanced with IC50 of 0.56g/mL whereas; the normal cells showed lower cytotoxicity with the IC50of 1.03g/mL [225]. Biosci. A novel drug delivery system based on carbon nanospheres for delivery of cancer therapeutics has been evaluated for internalization, and possible mechanism of endocytosis and biodistribution in mice [206]. FOIA Biomaterials 35(18), 49864995 (2014), L. Guo et al., Prostate cancer targeted multifunctionalized graphene oxide for magnetic resonance imaging and drug delivery. Before In this context, many studies have demonstrated that cellular interactions of polymer-based nanomaterials are highly influenced by their surface chemistry [120,121,122]. have used benzoic-imine bonds to attach -cyclodextrin directly to mesoporous silica nanoparticles (MSNs) which were partially hydrolyzed in the extracellular tumor space and completely hydrolysed inside endosomes with low pH ~5. Eur. In redox-activated drug release mechanism, a redox-responsive nanocarrier containing functional groups that reacts upon contact with oxidizing and/or reducing environment in and around cancer cells (peroxides, GSH, and free radicals), undergoing to chemical bond cleavage [63]. Heo et al., Gold nanoparticles surface-functionalized with paclitaxel drug and biotin receptor as theranostic agents for cancer therapy. Nanotechnology In Medicine: Huge Potential, But What Are The Risks? Soe et al., Folate receptor-mediated celastrol and irinotecan combination delivery using liposomes for effective chemotherapy. ChemMedChem 13(1), 7886 (2017), E. Voulgari et al., Synthesis, characterization and in vivo evaluation of a magnetic cisplatin delivery nanosystem based on PMAA-graft-PEG copolymers. Federal government websites often end in .gov or .mil. Mol. J. sharing sensitive information, make sure youre on a federal 2018;68:394. doi: 10.3322/caac.21492. Adv. Acad. Tailor-made nanomaterials functionalized with specific ligands can target cancer cells in a predictable manner and . Mater. 66, 225 (2014), D. Rosenblum et al., Progress and challenges towards targeted delivery of cancer therapeutics. To date, many types of organic nanocarriers have been developed such as liposomes, polymeric nanoparticles, dendrimers and micelles. Adv. Farooq et al., Gold nanoparticles-enabled efficient dual delivery of anticancer therapeutics to HeLa cells. Mater. 202, 513522 (2018), V.M. Mater. Chem. The in vitro studies indicated that the nanocarrier developed with docosahexaenoic acid, polyamide amine and conjugated with PTX had a better anticancer activity toward upper gastrointestinal cancer cells when compared to polyamide amine conjugated with PTX [276]. Endoplasmic retention effects vary with tumor types such that some cancers have wide epithelial fenestrations so that nanoparticles with broader size range can be effectively used. Nat. In fact, significant strides have been made towards the application of engineered nanomaterials for the treatment of cancer with high specificity, sensitivity and efficacy. Nat. Chem. J. Pharm. Sci. Smart Magnetic Drug Delivery Systems for the Treatment of Cancer. Chem. Small 6(1), 1221 (2010), R. Mout et al., Surface functionalization of nanoparticles for nanomedicine. This complexity allows a prompt reaction to the high concentration of stimuli, but not to low concentrations, achieving controlled specificity [65]. sharing sensitive information, make sure youre on a federal Artif. Shaikh et al., Liposome co-encapsulation of synergistic combination of irinotecan and doxorubicin for the treatment of intraperitoneally grown ovarian tumor xenograft. Scale bar: 200nm (b); in vitro cytotoxicity effect of different nanocomplexes on C6 cells evaluated by CCK8 assay at various TMZ concentrations. Mishra S, Bhatt T, Kumar H, Jain R, Shilpi S, Jain V. Front Pharmacol. C 89, 307315 (2018), C. Huang et al., Amphiphilic prodrug-decorated graphene oxide as a multi-functional drug delivery system for efficient cancer therapy. Release 200, 138157 (2015), C.K. Small 6(20), 22612265 (2010), Y.B. Table2 highlights various inorganic nanocarriers for delivery of anticancer therapeutics. J. Colloid Interface Sci. This pronounced variance from different surface coating suggests that chemical modification of nanoparticles is one of the most effectual means to control and restrain cellular interactions of nanomaterials, and hence their biological consequences. Nano Lett. These antitumor studies revealed that modified liposomes had lower systemic toxicity and prolonged the survival time of the treated mice by suppressing the tumor growth more strongly [234]. Thus, it is fundamental to engineer the nanomaterials to maximize their utility in biomedical applications. 111, 11061115 (2018), L. Ansari et al., Improved anticancer efficacy of epirubicin by magnetic mesoporous silica nanoparticles: in vitro and in vivo studies. Biomaterials 32(10), 25402545 (2011), S. Bhattacharyya et al., Efficient delivery of gold nanoparticles by dual receptor targeting. Expert Rev Mol Diagn. Today 19(3), 157168 (2016), A. Bajaj et al., Detection and differentiation of normal, cancerous, and metastatic cells using nanoparticle-polymer sensor arrays. 29(5), 65 (2018), W. Cheng et al., A drug-self-gated and tumor microenvironment-responsive mesoporous silica vehicle: four-in-one versatile nanomedicine for targeted multidrug-resistant cancer therapy. Correspondingly, these vehicles offer several other advantages including biocompatibility, self-assembly, and high drug cargo loading [231]. Spectrosc. Nano Lett. ACS Appl. J. Recently, a hybrid material based on graphene oxide (GO) coated with -cyclodextrin (CD) and poly(amido amine) dendrimer (DEN) was used to deliver doxorubicin, camptothecin (CPT) and a photosensitizer (protoporphyrin IX (PpIX)). Polym. Choi et al., Mechanism of active targeting in solid tumors with transferrin-containing gold nanoparticles. 46(43), 1483114838 (2017), N. Li et al., Curcumin-loaded redox-responsive mesoporous silica nanoparticles for targeted breast cancer therapy. Trewyn, V.S.Y. official website and that any information you provide is encrypted Also, these platforms can provide competent drug delivery systems responsive to various stimuli to enhance the therapeutic efficacy and reduce the side effects of loaded drugs. Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy. Uptake was less effective with the negatively charged particles, however, indicating the role of negative surface charge on the nanoparticles, which can reduce the undesirable clearance by liver cells [111]. Sci. Ovarian cancer (OC) is the seventh most common cancer in women worldwide. Nat Commun. Natl. Nanotechnology and Immunotherapy in Ovarian Cancer: Tracing - PubMed The cells are also counterstained with nuclear fast red. In vivo studies of MUC1 aptamer-capped mesoporous silica nanomaterials on MDA-MB-231 tumor-bearing Balb/c mice were found to effectively target breast cancer cells and induce a dramatic reduction in cell viability [223]. Nanomedicine and nanotoxicology: the pros and cons for Therefore, actively-targeted nanosystems need to be developed with extended blood circulation times and biocompatible profiles, along with neutral coating to prevent extensive non-specific binding of blood molecules. Various ligands such as antibodies, proteins, peptides, aptamers and small molecules have been used to target specific cells [268]. Specifically, cationic magnetic nanoparticles are retained by the cells for extended period, inducing no cytotoxicity [116]. Pharm. a The effect of IGF1R in MIAPaCa-2 cells was assessed by immunofluorescence labeling employing an anti-IGF1R antibody (shown in red color). Similarly, the cellular uptake and in vivo fate of micellar nanoparticles have been explored, wherein negatively charged micellar nanoparticles were taken up by tumor cells, and the mechanism of internalization was determined to occur through multiple distinct endocytic pathways including clathrin-mediated endocytosis, caveolae-mediated endocytosis, and macropinocytosis. Nanotechnol. In addition to the size of the nanomaterials, the shape of the nanomaterials is equally important in drug delivery. VR acknowledges the NIH (EB022641). Nat. Unauthorized use of these marks is strictly prohibited. Biogenic Ag nanoparticles can be employed against prostate and colon cancer. This vascularization displays spatial and temporal heterogeneity within and between tumor cells adding another level of challenges to passive targeting [38]. Nanotechnology has the potential to circumvent several drawbacks of conventional therapeutic formulations. pH-labile covalent bonds with benzoic-imine bond, 1,3,5-triazaadamantane (TAA) group, the hydrazone bond are developed as a proof of principle systems for pH-mediated response systems [67]. Howlader N, Noone AM, Krapcho M, Garshell J, Neyman N, Altekruse SF, Cronin KA, Howlander N, Aminou R. Waldron. Nanomed. Cancer Facts & Figures 2021 | American Cancer Society. Dalton Trans. Nano-based modalities provide enhanced transport across biological barriers, enable selective targeting ofmalignanttissues/cells, and offer strategies for sustained release of a drug [21, 22]. 129(27), 84388439 (2007), N.W.S. 10, 975999 (2015), T. Zhang et al., Polysialic acidpolyethylene glycol conjugate-modified liposomes as a targeted drug delivery system for epirubicin to enhance anticancer efficiency. 5(10), 2104721054 (2018), L. Zhang, Y. Li, C.Y. In another report, multi-walled carbon nanotube were decorated with TiO2Au nanocomposite, and the system was observed to be efficient in inducing toxicity to A549 and MCF7 cancer cell lines [200]. 12(8), 28112822 (2015), I.M. Rev. Release 172(3), 852861 (2013), S.K. Mesoporous silica nanomaterials (MSNs) have emerged as another class of drug delivery carriers, due to their surface properties such as large surface area, uniform porosity, stability, low toxicity and narrow size distribution [217]. Adv. Fa, folate; PCL, poly(-caprolactone); PEG, poly(ethylene glycol); PEI, poly(ethylenimine); TMZ, temozolomide. PMC J. Pharm. This review discusses numerous types of nanoparticles, targeting mechanisms, and approved nanotherapeutics for oncological implications in cancer treatment. Nanotechnol. 186, 122134 (2018), L. Qiu et al., Silver nanoparticles covered with pH-sensitive camptothecin-loaded polymer prodrugs: switchable fluorescence off or on and drug delivery dynamics in living cells. 90, 906913 (2017), V.R. 102, 555566 (2018), P. Gupta et al., Synthesis and in vitro studies of PLGA-DTX nanoconjugate as potential drug delivery vehicle for oral cancer. A wide range of nanotherapeutics, composed of organic and inorganic nanomaterialshave been developed with multiple types of drugs or molecules for cancer imaging, detection and treatment. Graphical illustration of passive and active drug targeting strategies. There is a multitude of other factors that can present potential challenges for nanotherapeutics such as low blood circulation rate in tumor vessels, tumor site macrophages, and extracellular matrices environment around tumor cells. Nanoscale 10(18), 85368546 (2018), N. Singh, A. Sachdev, P. Gopinath, Polysaccharide functionalized single walled carbon nanotubes as nanocarriers for delivery of curcumin in lung cancer cells. In summary, thephysicochemical properties such as size, shape, surface charge, and surface chemistry influence the mechanisms of cellular uptake, distribution and therapeutic nature of material. Drug packaging efficacy depends on encapsulation or drug conjugation efficiency. Cancer 105(4), 561567 (2003), R.B. Natl. J. Drug Deliv. Mater. Mater. Control. Fuster MG, Montalbn MG, Moulefera I, Vllora G, Kaplan DL. G4.0-polyamide amine-HEP-mPEG revealed precise release of doxorubicin and had prolonged retention compared to pristine doxorubicin in both Hela and fibroblast NIH3T3 cancer cells. Further, HKD appreciates the Centre for Advanced Materials and Industrial Chemistry (CAMIC) in the School of Sciences, RMIT University, Australia for an Honorary Visiting Research Fellowship. Other major nanomaterials that have noticeable contribution in drug delivery are carbon-based nanostructures and mesoporous silica nanoparticles. The advent of nanotechnology has revolutionized the arena of cancer diagnosis and treatment. Natl. J. Biotechnol. Eur. ACS Bio Med Chem Au. Similarly, mesoporous silica nanoparticles of different sizes (280, 170, 110, 50 and 30nm) were examined for the uptake by HeLa cells, revealing the maximum uptake by cells of 50nm sized mesoporous silica nanoparticles, showing the suitability to be used as carrier vehicles for drug delivery [105]. In the paradigm of nanomedicine, nanotechnology is being embraced to obtain effective drug delivery, establish novel in vitro diagnostics, and develop nano-based implants [7, 10, 11]. Small 7(10), 13221337 (2011), S. Krasnici et al., Effect of the surface charge of liposomes on their uptake by angiogenic tumor vessels. Since actively-targeted nanosystem rely on being in the vicinity of the target sites to home in and execute their functions, biodistribution profile is very critical to its proper functioning. Mater. Since tumor blood flow is low compared to observed in other organs and bodily tissues, the increased affinity based on the ligands cannot compensate for the clearance processes [32].
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