disadvantages of nanotechnology in cancer treatment

6, 286 (2015), B.S. J. Nanomed. Additionally, a newer generation of liposomes are emerging, focusing on redox sensitive liposomes, magnetic liposomes, enzyme sensitive liposomes and multifunctional smart liposomes [242,243,244,245]. 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. 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. Nanotechnology has the potential to circumvent several drawbacks of conventional therapeutic formulations. As illustrated in Fig. Wang et al., developed a multi-walled carbon nanotube platform with improved circulation half-life, and active targeting ability with high drug loading ratio. J. Pharm. J. Pharm. Release 172(3), 782794 (2013), C. Wong et al., Multistage nanoparticle delivery system for deep penetration into tumor tissue. 1. J. Nanomed. Biomaterials 33(3), 856866 (2012), A. Kumar et al., Gold nanoparticles functionalized with therapeutic and targeted peptides for cancer treatment. J. Nanomed. The use of diverse nanomaterials with desired properties and recent progress in the drug delivery arena have revealed outstanding challenges in cancer therapy and management. 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. Please enable it to take advantage of the complete set of features! It is anticipated that multiple drugs when delivered simultaneously to a cancer cell will exhibit a synergistic effect, when administered in an optimized ratio. Metal and metal oxide nanoparticles are one of the most useful materials as drug delivery vehicles due to their controllable size and shape, biocompatibility and easy surface functionalization. Bioconjug. We also discuss the current challenges and perspectives of nanomaterials in effective cancer management. In additionto functional groups on their branches, they are suitable for loading and binding diverse hydrophilic and hydrophobic drugs. However, some cons have also been noticed due to which the use of nanotechnology at a larger scale is not being encouraged. 527(1), 142150 (2017), Y. Huang et al., Superparamagnetic iron oxide nanoparticles conjugated with folic acid for dual target-specific drug delivery and MRI in cancer theranostics. The .gov means its official. Similarly accumulating a high degree of hydrophobicity on the nanoparticles led to increased susceptibility towards macrophage uptake, without offering a significant advantage for rapid target cell internalization [57]. The efficacy of a theranostics for prostate cancer has also been evaluated through in vitro and in vivo studies [141]. Int. Chem. Usually, targeting based approaches exploit the subtle differences in the expression of substrate molecules between cancer and normal cells. See this image and copyright information in PMC. Chem. This concentration difference on the cell surface is the basis for studies targeting cancer cells overexpressing EGFR [51, 52]. Similarly, graphene oxide with galactosylated chitosan with doxorubicin have been developed for the treatment of cancer. P. N. Navya or Hemant Kumar Daima. Clin. Adv. Temozolomide-FaPEC@siRNA exhibited higher cytotoxicity than both temozolomide-FaPEC and temozolomide-PEC, whereas C6 cells incubated with FaPEC@SCR and PEC@SCR exhibited viabilities over 90% even at a very high 100g/mL polymer concentration, indicating low cytotoxicity of carrier, a vital characteristic for in vivo application. Azhar NA, Abu Bakar SA, Citartan M, Ahmad NH. 60(11), 13071315 (2008), O.R. Control. J. Release 243, 342356 (2016), S. Sabnis et al., Superparamagnetic reconstituted high-density lipoprotein nanocarriers for magnetically guided drug delivery. 128, 1826 (2018), M.S.U. Rev. 151, 812820 (2016), J. Chen et al., One-step reduction and PEGylation of graphene oxide for photothermally controlled drug delivery. 12(1), 320 (2018), S.-I. A summary of different organic nanomaterials used as drug delivery carrier for anticancer drugs and the targets is shown in Table3. 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. 334(2), 196201 (2013), K. Saha et al., Gold nanoparticles in chemical and biological sensing. J. Pharm. Eur. Biomacromolecules 14(8), 26012610 (2013), A. Jose et al., Temperature-sensitive liposomes for co-delivery of tamoxifen and imatinib for synergistic breast cancer treatment. Eur J Pharm Biopharm. Sahoo, Evaluation of curcumin loaded chitosan/PEG blended PLGA nanoparticles for effective treatment of pancreatic cancer. Int. Chem. Specifically, the use of nanocarriers for drug delivery offers many advantages; (i) circumvent the problems of solubility and stability of anticancer drugs; (ii) prevents the drug from degradation from proteases and other enzymes and increase the half-life of the drug in the systemic circulation; (iii) improves drug distribution and targeting; (iv) helps in the sustained release of drug by targeting the cancer sites and (v) helps in delivery of multiple drugs and, therefore helps inreducing drug resistance [23]. Rompicharla et al., Octa-arginine modified poly(amidoamine) dendrimers for improved delivery and cytotoxic effect of paclitaxel in cancer. have developed different shaped mesoporous silica nanoparticles (sphere, rod, and long rod) functionalized with fluorescein isothiocyanate (FITC) and rhodamine B isothiocyanate (RITC) for imaging and quantification of mesoporous silica nanoparticle uptake. [222] have developed macroporous silica nanoparticles with a peptide loading efficiency of 40%, which upon administration induced apoptosis. Mater. Finally, we attempt tosummarize the current challenges in nanotherapeutics and provide an outlook on the future of this important field. Introduction. Adv. The physicochemical properties of nanomaterials play a significant role in the biocompatibility, and toxicity in the biological systems [284, 285]. NanoBiotechnology 3(1), 4045 (2007), A. Verma, V.M. Current chemotherapy faces problems such as lack of specificity, cytotoxicity, induction of multi-drug resistance and stem-like cells growth. Chem. Proc. The influence of surface coating on the toxicity and cellular uptake of Au nanorods were studied revealing the surface chemistry dependent cellular uptake of Au nanorods covered with poly(diallyldimethylammonium chloride) [PDDAC] [127]. Ferritin: A Promising Nanoreactor and Nanocarrier for Bionanotechnology. C 89, 274282 (2018), D. Wang et al., Facile preparation of doxorubicin-loaded and folic acid-conjugated carbon nanotubes@poly(N-vinyl pyrrole) for targeted synergistic chemo-photothermal cancer treatment. 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. Recently, coreshell nanoparticles were also developed with a magnetic core and mesoporous silica nanomaterials shell to effectively deliver epirubicin. 8(5), 565580 (2011), L. Sercombe et al., Advances and challenges of liposome assisted drug delivery. The cellular entry of nanomaterials depends on surface charge [109]. Nanoparticle-Based Drug Delivery in Cancer Therapy and Its Role in Overcoming Drug Resistance. Nanotechnology in cancer diagnosis: progress, challenges and opportunities In the fight against cancer, early detection is a key factor for successful treatment. Most cognate substrates for nanoparticles bound ligands are present in the extravascular space of tumor outside of the blood vessels epithelial lining. ACS Appl. B Biointerfaces 111, 117123 (2013), S. Aryal, C.-M.J. Hu, L. Zhang, Polymercisplatin conjugate nanoparticles for acid-responsive drug delivery. Epub 2020 Oct 16. Eng. 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]. Current trends and challenges in cancer management and therapy using designer nanomaterials, https://doi.org/10.1186/s40580-019-0193-2, http://creativecommons.org/licenses/by/4.0/. Cancer Res. Nano Lett. Due to the advancements in nanomedicine, several nanoparticle formulations have been developed for co-deliveryof cancer chemotherapeutics [270, 271]. The biodistribution profile is also strongly influenced by active clearance processes posed by various immune cells, and blood flow/renal filtration rate. 4(2), 113121 (2015), B. Kumar et al., In vitro evaluation of silver nanoparticles cytotoxicity on Hepatic cancer (Hep-G2) cell line and their antioxidant activity: green approach for fabrication and application. The study also demonstrated the detection of residual tumors following intraperitoneal therapy signifying the possibility of image-guided surgery to remove drug-resistant tumors [159]. The graphene oxide based carrier was found to be effective in inhibiting and killing A549 cells, and displayed lesser toxicity against normal human bronchial epithelial cells [215]. 33(10), 23732387 (2016), J.-H. Park et al., Hyaluronic acid derivative-coated nanohybrid liposomes for cancer imaging and drug delivery. Mater. J. e In vitro cytotoxicity of unconjugated and conjugated doxorubicin in MIA PaCa-2 cells. Chan, Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells. Sci. 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. Oncol. 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. Epub 2014 Aug 9. Int. 45(6), 10821091 (2017), Z. Muhammad et al., PEG capped methotrexate silver nanoparticles for efficient anticancer activity and biocompatibility. Mater. Thus, nanotechnology is creating new opportunities for designing materials that can revolutionize the approaches to drug delivery and transform the landscape of the pharmacological treatment of cancer [7, 24,25,26]. From the discussion above, it is evident that the surface charge of the nanomaterials affects their cellular uptake, and these particles can be efficiently used in cancer treatment based on the cell type and mechanism of endocytosis. 129(32), 98569857 (2007), G. Han, P. Ghosh, V.M. However, the design of effective cancer nanotherapeutics remains a great challenge, and only a few nanoformulations have entered clinical trials. 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. Release 277, 89101 (2018), Y.J. It is evident that mesoporous silica nanomaterials are one of the promising nanocarriers for efficient delivery of cancer therapeutics due to their useful properties. Daima et al., Synergistic influence of polyoxometalate surface corona towards enhancing the antibacterial performance of tyrosine-capped Ag nanoparticles. Mater. 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. They have measured the cumulative release of loaded doxorubicin drug in different pH concentrations to confirm the functionality of the system [68]. -, The, L., LANCET, (2018) 392, 985. Pharm. J. Pharm. Biomaterials 31(3), 438448 (2010), E.C. CAS Mangadlao et al., Prostate-specific membrane antigen targeted gold nanoparticles for theranostics of prostate cancer. Nat. Kim et al., Entrapment of hydrophobic drugs in nanoparticle monolayers with efficient release into cancer cells. Polymeric nanoparticles are colloidal nanoparticles wherein therapeutic molecules will be encapsulated or adsorbed or conjugated in the polymer matrix. 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. 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]. Sci. Due to the lack of understanding of toxicity and in vivo behaviour of nanoformulations, clinical trials are experiencing major setbacks. B Biointerfaces 75(1), 118 (2010), F. Masood, Polymeric nanoparticles for targeted drug delivery system for cancer therapy. Biomed. There was a 27% increase in the cellular uptake of cells treated with magnetic mesoporous silica nanomaterials with epirubicin in the presence of external magnetic field when compared to free epirubicin [226]. Am. Biotechnol. Recently, a theranostic nanoparticle to enhance intra-tumoral drug delivery by overcoming drug resistance and providing image-guided drug delivery by reducing the systemic toxicity was developed using iron oxide nanoparticles. 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 . 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. Cellular uptake of larger particles (50nm spheres and 40nm stars) was higher when compared to 13nm spheres, establishing that the size and shape of the nanoconstructs not only influenced the kinetics of cellular uptake but also affected intracellular distribution as depicted in Fig. sharing sensitive information, make sure youre on a federal Folic Acid-Modified Ibrutinib-Loaded Silk Fibroin Nanoparticles for Cancer Cell Therapy with Over-Expressed Folate Receptor. 10, 51235137 (2015), Z.C. J. Pharm. Mol. Chem. 8c, the cell viability of various formulations was investigated on a rat C6 glioma cell line at different temozolomide concentrations. Persistent insoluble particles in in the environment can have far bigger negative effects than those revealed by human health assessments. B 3(39), 77247733 (2015), J. Zhang et al., pH-sensitive polymeric nanoparticles for co-delivery of doxorubicin and curcumin to treat cancer via enhanced pro-apoptotic and anti-angiogenic activities. Chem. An official website of the United States government. Generally, only small quantities of nanomedicine are used for pre-clinical and clinical trial studies. Kuruvilla et al., Dendrimerdoxorubicin conjugates exhibit improved anticancer activity and reduce doxorubicin-induced cardiotoxicity in a murine hepatocellular carcinoma model. Surface modified polylactic acid (PLA) nanoparticles have been reported and employed for delivery of docetaxel (DTX) as a targeted drug delivery system for the treatment of liver cancer. Sci. Choi et al., Mechanism of active targeting in solid tumors with transferrin-containing gold nanoparticles. pp. California Privacy Statement, 5 [103]. A few current strategies are based on the chemistry programmed into the nanosystems that are responsive towards pH or temperature, erosion due to the local chemical environment, redox reaction-based release, and enzyme-mediated release as discussed below [62]. Cite this article. The CFPAC-1 pancreatic adenocarcinoma cell viability decreased, indicating a PEGc polyamide amine-PEG dendrimers anti-cancer effect. Pept. Chung et al., The effect of surface functionalization of PLGA nanoparticles by heparin- or chitosan-conjugated Pluronic on tumor targeting. Nanomedicine and nanoparticle-based delivery systems in plastic and reconstructive surgery. Mater. Nanotechnology for cancer diagnostics: promises and challenges.

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