disadvantages of nanotechnology in cancer treatment

Nanomedicine 2(1), 113123 (2007), G. Han et al., Drug and gene delivery using gold nanoparticles. Correspondingly, these vehicles offer several other advantages including biocompatibility, self-assembly, and high drug cargo loading [231]. The noble metal nanostructures, particularly Au nanoparticles, are widely used for delivering drugs [140,141,142]. Res. Sci. Apart from folate-mediated targeting, aptamer-functionalized PEG-PLGA nanoparticles have also been constructed for anti-glioma drug delivery by active targeting the tumor. Nat. Res. 359(17), 1834 (2008), X. Li et al., Enhancement of cell recognition in vitro by dual-ligand cancer targeting gold nanoparticles. Rotello, Sniffing out cancer using chemical nose sensors. Pharmacol. 24(40), 54765480 (2012), Z.J. Many such formulations have been approved [34], opening new avenues toward cancer therapeutics. 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. 49(1), 160172 (2014), P.K.B. Chem. Acta A Mol. 7a. Springer Nature. Clearly, carbon-based nanomaterials have led to the improvement in cancer therapy due to their unique properties. Ind. Evol. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). have demonstrated that the internalization of magnetic nanoparticles inside HeLa cells is dependent on the nanoparticle surface charge and incubation time. Specifically, the lack of in vitro/in vivo correlation of drug release profiles is a major lingering issue. Later liposomes were PEGylated (PLS) by a PEG-lipid post-insertion technique followed by covalent coupling with lactoferrin (Lf) to the surface of liposomes as illustrated in Fig. Macromol. 2020 Dec 15;591:119986. doi: 10.1016/j.ijpharm.2020.119986. Cancer Res. 2(12), 751 (2007), D.B. Polym. Biol. Colloids Surf. Biotechnol. Lu et al., Magnetic graphene oxide for dual targeted delivery of doxorubicin and photothermal therapy. These in vitro and in vivo studies confirmed the effectiveness of combination therapy using temozolomide and siRNA for treatment of glioma and provided understanding on the folate targeted co-delivery of cancer therapeutics. The solubility, biodistribution and resistance of anticancer drugstogether form a significant hurdle in improving the pharmacodynamic profile for the treatment of cancer. Mater. Integr. Macromol. Liposomes can be conjugated with poly(ethylene glycol) (PEG), targeting ligands and/or antibodies, polysaccharides on the external surface to enhance solubility, to increase the hydrophilicity and to provide passive and active targeting functions, in due course attaining high drug efficiency with low toxicity [233]. Thus, the nanomaterials used for targeting tumor cells should have the capability of increasing local concentration of the drugs in and around tumor cells, thereby reducing the potential toxicity toward healthy cells [27]. But these problems may be from the chemotherapy drugs they. Int. 12(4), 11931202 (2015), S. Zhai et al., Visible light-induced crosslinking and physiological stabilization of diselenide-rich nanoparticles for redox-responsive drug release and combination chemotherapy. by A. Dhawan (CRC Press, Boca Raton, 2018), pp. Federal government websites often end in .gov or .mil. Spoial A, Ilie CI, Motelica L, Ficai D, Semenescu A, Oprea OC, Ficai A. Nanomaterials (Basel). The pH dependent release studies indicated the drug release was greater at pH 5.5 than pH 7.4 and could effectively target epidermal growth factor receptor-expressing CT-26 murine colorectal cells. 132(3), 10181022 (2010), P. Ghosh et al., Gold nanoparticles in delivery applications. Nanoparticles are classified into several main categories. Terms and Conditions, Furthermore, the manufacturing of nanomedicine products for commercialization is a key obstacle, as large scale-production is technically challenging. The ex vivo permeability of these formulations tested on mice dorsal skin and in vivo anticancer activity were evaluated in A431 tumor-bearing mice. 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. 47(2), 514532 (2018), T. Dichwalkar et al., Omega-3 fatty acid grafted PAMAM-paclitaxel conjugate exhibits enhanced anticancer activity in upper gastrointestinal cancer cells. Recently, nanotechnology and nanoparticles have attracted great interest in cancer therapeutics as they can provide improved and targeted drug delivery systems to overcome the drawbacks of conventional chemotherapy. In fact, significant strides have been made towards the application of engineered nanomaterials for the treatment of cancer with high specificity, sensitivity and efficacy. Recently, nanographene oxide complexed with upconverting nanoparticles were used for tumor imaging and photothermal therapy, signifying the potential of multifunctional graphene for clinical antitumor treatments [213]. Biomed. The surface charge of the nanoparticles is one of the leading factors to direct the interaction at the nano-bio interface [23]. J. Pharm. There was 29-fold increase in therapeutic efficacy of the nanocarrier during the combination therapy when compared to control. eCollection 2022 Jun 15. Biosci. Eng. Multifunctional graphene smart nanomaterials have been developed for drug delivery and cellular imaging in cancer treatment [210, 213]. Evaluating intrinsic and non-intrinsic cancer risk factors. Med. The chemical changes can also introduce changes in the hydrophobicity of the polymer, changing the integrity of nanoparticles and thereby leading to release of drug cargo. https://doi.org/10.1186/s40580-019-0193-2, DOI: https://doi.org/10.1186/s40580-019-0193-2. Kim et al., Entrapment of hydrophobic drugs in nanoparticle monolayers with efficient release into cancer cells. The delivery of PEGylated multi-walled carbon nanotubes conjugated with doxorubicin efficiently released 57% of the drug at lower pH within 24h, and could inhibit HepG2 cells when compared to free doxorubicin [204]. The extracellular microenvironment of tumor tissues is acidic, due to secreted lactic acid caused by glycolysis in anorexia. J. Pharm. 34, 7000 (2016), V.P. 12, 77637776 (2017), Y. Li et al., Polyethylenimine-functionalized silver nanoparticle-based co-delivery of paclitaxel to induce HepG2 cell apoptosis. In vivo, pharmacokinetic studies have also been conducted in the study to reveal the variation in the glioma growth in rat brain for different complexes after 25days of the first injection. J. Biomed. Would you like email updates of new search results? There are two categories of nanosystems, open-loop control systems and closed-loop control systems, grouped according to what activation factors stimulate drug release as schematically shown in Fig. 550(1), 170179 (2018), H. Gan et al., Enhanced delivery of sorafenib with anti-GPC3 antibody-conjugated TPGS-b-PCL/pluronic P123 polymeric nanoparticles for targeted therapy of hepatocellular carcinoma. Rev. HHS Vulnerability Disclosure, Help C 82, 291298 (2018), C. Chittasupho, S. Anuchapreeda, N. Sarisuta, CXCR284 targeted dendrimer for anti-cancer drug delivery and breast cancer cell migration inhibition. Dalton Trans. Nature 196(4853), 476 (1962), S.K. Photobiol. Chem. Mol. 8600 Rockville Pike Daima et al., Complexation of plasmid DNA and poly(ethylene oxide)/poly(propylene oxide) polymers for safe gene delivery. These studies do raise concerns about how an appropriate optimization of targeting moieties, conjugation approaches and densities play an essential role in the desired outcomes of the therapeutic nanosystems. Eng. Nanotechnology has the potential to facilitate the transport of drugs across the blood-brain barrier and to enhance their pharmacokinetic profile. Nanotechnology-based delivery systems hold the potential to overcome such limitations. Release 243, 342356 (2016), S. Sabnis et al., Superparamagnetic reconstituted high-density lipoprotein nanocarriers for magnetically guided drug delivery. Acad. have proposed a multi-factorial nanosystem that changes size upon reaching different locations of the tumor sites. All the authors have made substantial intellectual contribution in the preparation of the manuscript. Additionally, mesoporous silica nanomaterials can release cargo in response to stimuli. Nanotechnol. ACS Appl. Nanotechnology improves cancer detection and, Nanotechnology improves cancer detection and diagnosis, Schematic illustration of nanotechnology applications, Schematic illustration of nanotechnology applications in cancer diagnosis, MeSH For example, epidermal growth factor receptor (EGFR, responsible for epithelial tissue development and homeostasis) is overexpressed in cancerous cells relative to normal cells, as cancer cells grow and divide vigorously [50]. 11, 20212037 (2016), K. Vimala et al., Green synthesized doxorubicin loaded zinc oxide nanoparticles regulates the Bax and Bcl-2 expression in breast and colon carcinoma. ACS Nano 3(2), 307316 (2009), S.R. Cancer Res. Nanotherapeutics are The % of viable cells after 96h incubation with IGF1 or IGF1-IONPs, and for 4h at equivalent IGF1 concentrations was estimated by cell proliferation assay, wherein *P<0.05; **P<0.001. d The in vivo effect on tumor cell proliferation of IGF1-IONPs in human pancreatic PDX-tumor xenografts. However, there are multiple factors thatneed to be optimized for effective use of active-targeted cancer therapeutics. 5(13), 16271637 (2016), F. Li et al., Near-infrared light stimuli-responsive synergistic therapy nanoplatforms based on the coordination of tellurium-containing block polymer and cisplatin for cancer treatment. Nanotechnology in cancer diagnosis: progress, challenges and opportunities In the fight against cancer, early detection is a key factor for successful treatment. Similarly, mesoporous silica nanoparticles coated with different functional groups resulted in different mechanisms of endocytosis by HeLa cells, providing evidence of surface functional group-dependent uptake [129]. 41(7), 25392544 (2012), R. Weissleder et al., Cell-specific targeting of nanoparticles by multivalent attachment of small molecules. Nanoconstructs for theranostic application in cancer: Challenges and strategies to enhance the delivery. Nanoparticles are classified into several main categories. Target substrates can be surface molecules expressed in diseased cells, proteins, sugars or lipids present in the organs, molecules present (or secreted by tumor cells) in the microenvironment of the diseased cells or even the physicochemical environment in the vicinity [46]. Chemical affinity for active targeting is based on different specific molecular interactions such as receptorligand-based interactions, charge-based interactions and facilitated motif-based interactions with substrate molecules [41, 42]. 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]. Mater. Various therapeutic implications of nanoformulations have created brand new perspectives for cancer treatment. C 75, 182190 (2017), M. Alibolandi et al., Smart AS1411-aptamer conjugated pegylated PAMAM dendrimer for the superior delivery of camptothecin to colon adenocarcinoma in vitro and in vivo. 2 [29]. Am. Safwat et al., Fluorouracil-loaded gold nanoparticles for the treatment of skin cancer: development, in vitro characterization, and in vivo evaluation in a mouse skin cancer xenograft model. Finally, the surface charge significantly affects the internalization process and the cellular endocytosis mechanism as discussed above [112]. FOIA C 70, 763771 (2017), S. Bano et al., Smart nickel oxide based coreshell nanoparticles for combined chemo and photodynamic cancer therapy. Netala et al., Biogenesis of silver nanoparticles using leaf extract of Indigofera hirsuta L. and their potential biomedical applications (3-in-1 system). Biotechnol. Scheme representing the formulation of doxorubicin loaded PEGylated liposome, and doxorubicin loaded lactoferrin modified PEGylated liposome (a); effect of cell viability of free DOX and the liposomal formulations evaluated by MTT assay in HepG2, BEL7402, and SMMC7721 cells at different time intervals (b); relative tumor volume of various liposomal formulations injected to tumor-bearing mice through tail veins every 7days at a dose of 5mg/kg DOX (c); change in the body weight of tumor-bearing mice after each treatment (d); image of tumors excised on 21st day from each treatment group (e); relative tumor volume at the time of sacrifice from each treatment group (f); tumor weight at the time of sacrifice from each treatment group (g). Eur J Pharm Biopharm. J. Pharm. Drug Deliv. However, limitations such as lack of specificity, cytotoxicity, and multi-drug resistance pose a substantial challenge for favorable cancer treatment. 132(13), 46784684 (2010), I. 22(27), 1377313781 (2012), Y. Wang et al., Graphene oxide covalently grafted upconversion nanoparticles for combined NIR mediated imaging and photothermal/photodynamic cancer therapy. J. Pharm. 2023 Mar 30;45(1):15. doi: 10.1186/s40902-023-00383-9. Messersmith, D.J. Miranda et al., Array-based sensing of proteins using conjugated polymers. (n.d.). FOIA J. Nanomed. Table1 presents different nanocarriers loaded with drugs that are released to tumor sites based on specific stimuli. Similarly, complete tumor eradication has been achieved employing cut-single walled carbon nanotubes coated with BSA-reduced Au nanoparticles, enhancing doxorubicin drug release when combined with phototherapy with an 808nm laser in a nude mouse model [202]. These nanoparticles can be customized for various biomedical applications due to their unique characteristics such as drug solubility, stability, and preferential accumulation [267]. The nanocarriers need to be smaller than the cut-off of the proportions in the neovasculature, with the extravasation to the tumor acutely affected by the size of the vehicle. Res. Invest. Release 133(1), 23 (2009), Article Chem. Nanotechnol. Funct. Nanobiosensors for evaluating ovarian cancer biomarkers can be categorized based on electrochemical, optical . a The effect of IGF1R in MIAPaCa-2 cells was assessed by immunofluorescence labeling employing an anti-IGF1R antibody (shown in red color). Pharm Res. Google Scholar, M.U.R. Rapid Commun. Oncogene 34, 3215 (2014), J. Zhao, V. Castranova, Toxicology of nanomaterials used in nanomedicine. Biomaterials 31(3), 438448 (2010), E.C. PMC Daima, Nanomedicine in sensing, delivery, imaging and tissue engineering: advances, opportunities and challenges. Koklesova L, Jakubikova J, Cholujova D, Samec M, Mazurakova A, udomov M, Pec M, Hassan STS, Biringer K, Bsselberg D, Hurtova T, Golubnitschaja O, Kubatka P. Front Pharmacol. Usually, targeting based approaches exploit the subtle differences in the expression of substrate molecules between cancer and normal cells. 12(2), 251259 (2012), A. Agostini et al., A photoactivated molecular gate. New opportunities for nanoparticles in cancer immunotherapy. 12(11), 958 (2013), H. Lee et al., In vivo distribution of polymeric nanoparticles at the whole-body, tumor, and cellular levels. All these observations are motivating and may change the face of cancer treatment and management. For example, in poly(propylene sulfide) polymer nanoparticles, disulfide bonds act as a redox-responsive motif, and upon reacting with H2O2 leads to a change of hydrophobicity of the polymers causing a collapse of nanoparticles and thus drug release [64]. Various ligands such as antibodies, proteins, peptides, aptamers and small molecules have been used to target specific cells [268]. Several strategies have also been developed to accomplish liposomal codelivery of chemotherapeutic agents. Cancer is a disease with complex pathological process. 30(45), 299315 (2009), Y. Kato et al., Acidic extracellular microenvironment and cancer. 122, 311330 (2018), H.K. It is evident that mesoporous silica nanomaterials are one of the promising nanocarriers for efficient delivery of cancer therapeutics due to their useful properties. 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. Int. Sun et al., Temperature-sensitive gold nanoparticle-coated pluronic-PLL nanoparticles for drug delivery and chemo-photothermal therapy. A wide range of materials have been used to develop nanocarriers. Biomaterials 32(31), 80108020 (2011), S. Mignani et al., Dendrimers in combination with natural products and analogues as anti-cancer agents. Soc. Eur. Int. Google Scholar, X. Gao et al., In vivo cancer targeting and imaging with semiconductor quantum dots. Cite this article. Artif. Biosci. Int. Redox-response moieties can also respond to the stimuli in a non-linear fashion. 8600 Rockville Pike 67(4), 1555 (2007), S.M. -. 12(8), 28112822 (2015), I.M. The targeting of cells by nanoparticles results in highly specific delivery of cargos, resulting in high concentrations of the therapeutic within the cell. To date, many types of organic nanocarriers have been developed such as liposomes, polymeric nanoparticles, dendrimers and micelles. Redox activated polymeric nanoparticles in tumor therapy (Elsevier, Amsterdam, 2017). Mater. Rev. Biotechnol. Chem. Xia et al., constructed a pH sensitive liposome formulation by loading tariquidar (TQR) and doxorubicin to overcome multidrug resistance of drug-resistant ovarian cancer cells. This is known as enhanced permeability and retention (EPR) effect, which is the basis of passive targeting [31]. Intervention of nanotechnology has revolutionized the therapy of lung cancer upto a great extent by overcoming the current constraints in conventional therapies. Artif. Biomed. Likewise, Huang et al. 2006 May;6(3):307-18. doi: 10.1586/14737159.6.3.307. Eur. 10, 157168 (2015), M. Ajmal et al., Synthesis, characterization and in vitro evaluation of methotrexate conjugated fluorescent carbon nanoparticles as drug delivery system for human lung cancer targeting. This review discusses numerous types of nanoparticles, targeting mechanisms, and approved nanotherapeutics for oncological implications in cancer treatment. 24(17), 24502461 (2013), M. Ma et al., Bi2S3-embedded mesoporous silica nanoparticles for efficient drug delivery and interstitial radiotherapy sensitization. Rev. The challenge of bench-to-bedside translation of dendrimers, however, remains a significant challenge. Nano Res. In contrast, in closed-loop systems the drug release rate is controlled by the presence and intensity of internal stimuli in the vicinity of the target sites [60, 61]. 58, 349364 (2017), Y. Peng et al., Codelivery of temozolomide and siRNA with polymeric nanocarrier for effective glioma treatment. 17(8), 1600457 (2017), K. Jain et al., Dendrimer toxicity: lets meet the challenge. The cellular uptake of surface modified PLGA nanoparticles were in the order of vitamin E TPGS-coated PLGA>PVA-coated PLGA>naked PLGA nanoparticles [124]. Nanotechnology provides high sensitivity, specificity, and multiplexed measurement capacity and has therefore been investigated for the detection of extracellular cancer biomarkers and cancer cells, as well as for in vivo imaging. Mater. pp. An official website of the United States government. Mater. 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. Process Biochem. Sci. Kim et al., Co-eradication of breast cancer cells and cancer stem cells by cross-linked multilamellar liposomes enhances tumor treatment. Sci. In fact, most of our current knowledge is based on a few subcutaneous tumor xenograft models that divide vigorously resulting in very high EPR effects. Adv. Drug Deliv. Mater. Eng. Int. Graphene and its derivatives comprise an important class of materials that is widely used in drug and gene delivery, cell imaging, photothermal cancer therapy and biosensing [207,208,209,210]. Federal government websites often end in .gov or .mil. J. Photochem. Thus, to mitigate the problems associated with nanomaterial-based therapeutic agents for cancer treatment, design and development strategies need to be employed before they are used in medicine for better treatment and human life. Med. The smart design and synthesis of a library of nanomaterials, precise control over their physicochemical properties and ease of their surface functionalization to increase specificity is indeed necessary for the success of cancer nanotherapeutics. Natl. Nanoparticle-Based Drug Delivery in Cancer Therapy and Its Role in Overcoming Drug Resistance. Rev. Biol. 529(1), 102115 (2017), J.N. Soybean phosphatidylcholine/cholesterol was used in the molar ratio of 3:2 to prepare liposomes by thin film hydration method, and doxorubicin was remotely loaded into the liposomes via the ammonium gradient method. Nanomed. 7, 653 (2010), S.K. 26(6), 876885 (2018), S. Nicolas et al., Polymeric nanocapsules as drug carriers for sustained anticancer activity of calcitriol in breast cancer cells. The study has shown the sustained and pH-dependent release, in which the volume of the tumor reduced compared tothe untreated control. California Privacy Statement, Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy. Areas covered: Nanoparticles (NPs) used as drug delivery vehicles consist of. Moreover, the involvement of complicated multi-stage processes of production of nanotherapeutics and the high cost of raw materials renders these nanotherapeutics an expensive option. In this review, we discuss the development of smart nanomaterials for treating cancer, with emphasis on the strategies of drug targeting and triggering sustained release of drug from the nanocarriers. Control. Chou, I.M. Biophys. Offers up-to-date information on the target therapies used in cancer treatment. Disclaimer. B Biointerfaces 133, 246253 (2015), A. Kaphle, N.P. J. Pharm. 127(36), 1249212493 (2005), Z. Liu et al., Carbon nanotubes in biology and medicine: in vitro and in vivo detection, imaging and drug delivery. J. J. Liposome Res. To ascertain this dependence, three different sizes and two different shapes (13nm sphere, 50nm sphere and 40nm star) of siRNA-conjugated gold nanoconstructs were developed to check the in vitro response of U87 glioblastoma cells targeting the expression of isocitrate dehydrogenase 1. [222] have developed macroporous silica nanoparticles with a peptide loading efficiency of 40%, which upon administration induced apoptosis. Angew. Mater.

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