disadvantages of nanotechnology in cancer treatment

Int. 2017;37:1. Moreover, nanomaterials can also be designed for increased drug loading, improved half-life in the body, controlled release, and selective distribution by modifying their composition, size, morphology, and surface chemistry. Rezaianzadeh A, Jalali M, Maghsoudi A, Mokhtari AM, Azgomi SH, Dehghani SL. Finally, we attempt tosummarize the current challenges in nanotherapeutics and provide an outlook on the future of this important field. Cancer; Cellular targeting; Chemotherapy; Cryosurgery; Multidrug resistance; Nanoparticles; Scale-up. Cells Nanomed. Mater. Various ligands such as antibodies, proteins, peptides, aptamers and small molecules have been used to target specific cells [268]. Provided by the Springer Nature SharedIt content-sharing initiative. Science 267(5202), 1275 (1995), A. Bajaj et al., Array-based sensing of normal, cancerous, and metastatic cells using conjugated fluorescent polymers. -. Photobiol. have reported the in vitro anticancer effects of docetaxel conjugated Au doped apatite. 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. Mater. C 91, 395403 (2018), G. Arya, M. Das, S.K. J. Nanomed. [106] have studied the effect of the shape of Au nanoparticles (rod and spherical) on cellular uptake and established that the nanoparticles uptake is shape and size dependent, with uptake of spherical nanoparticles efficient compared to their rod-shaped counterparts. It could also highlight a tumor's parameters and margins to enhance the precision of diagnostics. Spectrosc. 127(36), 1249212493 (2005), Z. Liu et al., Carbon nanotubes in biology and medicine: in vitro and in vivo detection, imaging and drug delivery. This phenomenon can be further exploited for potential therapeutic purposes, employing nanoparticles as drug or gene delivery carriers. These structures can be produced by using macromolecules such as polyamide amine (PAMAM), polypropyleneimine and poly(aryl ether). Daima, Nanomedicine in sensing, delivery, imaging and tissue engineering: advances, opportunities and challenges. California Privacy Statement, IET Nanobiotechnol. J. Pharm. 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. Theranostics 8(3), 693709 (2018), G. Wang et al., Theranostic hyaluronic acid-iron micellar nanoparticles for magnetic-field-enhanced in vivo cancer chemotherapy. Chem. For instance, Ag nanoparticles synthesized using Indigofera hirsuta leaf extract and pollen extract of Phoenix dactylifera showed dose-dependent cytotoxicity against different cancers [149, 150]. Nature 196(4853), 476 (1962), S.K. 23(11), 14181423 (2005), D. Peer et al., Nanocarriers as an emerging platform for cancer therapy. Eur. Therefore, Nanotoxicology a branch of nanomedicine has emerged as an essential field of research, paving the way for the assessment of toxicity of nanoparticles. Release 143(3), 374382 (2010), S.A. Kulkarni, S.-S. Feng, Effects of particle size and surface modification on cellular uptake and biodistribution of polymeric nanoparticles for drug delivery. Chem. Finally, the surface charge significantly affects the internalization process and the cellular endocytosis mechanism as discussed above [112]. Biomaterials 26(15), 27132722 (2005), D.N. In this context, Chittasupho et al., have developed CXCR4 targeted dendrimer for breast cancer therapy. Chem. Sci. 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Decuzzi et al., Size and shape effects in the biodistribution of intravascularly injected particles. Several polymer-based therapeutics are currently in the market or undergoing a clinical evaluation to treat cancer. Cancer Facts & Figures 2021 | American Cancer Society. Current mainstay treatment of cancer includes surgery, radiotherapy and chemotherapy, among which chemotherapy has been widely performed in clinic because of its simple and convenient process [1,2].However, there are still some significant limitations in cancer treatment using chemotherapy only. 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]. J. Pharm. Sci. Mater. In addition, many other factors have a profound consequence on nanomaterials uptake and distribution in cells. Biol. Sci. Mater. These nanoparticles can be synthesized using synthetic and natural polymers, and have been extensively used in drug delivery applications [265, 266]. 2022 Mar 1;2(3):258-281. doi: 10.1021/acsbiomedchemau.2c00003. Intervention of nanotechnology has revolutionized the therapy of lung cancer upto a great extent by overcoming the current constraints in conventional therapies. Modulating rate of drug release in response to an activation signal constitutes an essential strategy to achieve controlled release purposes as well as maintaining effective therapeutic dosage over a stretch of time. The design of highly efficient nanocarriers that meet the requirements for a drug delivery vehicle is an intricate process. Chem. Would you like email updates of new search results? Therapeutic efficacy of passive targeted approaches is limited by the heterogeneity of the EPR effects seen within and between different tumors. 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. Eur. Nat. J. Pharm. Biotechnol. Diverse biomolecules can constitute a ligand, including antibodies, proteins, nucleic acids, peptides, carbohydrates and small organic molecules such as vitamins [43,44,45]. The https:// ensures that you are connecting to the Carbon-based nanomaterials have also been extensively studied in imaging, delivery and diagnosis of cancer, due to their attractive characteristics such as high surface area, high drug loading capacity, and easily modifiable surfaces [7, 192,193,194,195,196,197]. 516, 332341 (2018), M. Manzano, M. Vallet-Reg, Mesoporous silica nanoparticles in nanomedicine applications. Bethesda, MD 20894, Web Policies Mater. Similar to Au nanoparticles,silver (Ag) nanoparticles havealso been demonstrated to be used as anticancer agents for the treatment of multiple types of cancer [144,145,146,147]. 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. 2023 Mar 25;11(4):733. doi: 10.3390/vaccines11040733. Biomaterials 32(33), 85488554 (2011), C.H.J. Ag nanoparticles conjugated with phytopharmaceuticals can serve as non-toxic delivery vehicles, contrast agents and photothermal agents for cancer therapy. Emerging evidence has also shown that nanoparticles have the . Also, difficulties in the approval will tend to increase due to the development of multifunctional nanoplatforms. Apart from folate-mediated targeting, aptamer-functionalized PEG-PLGA nanoparticles have also been constructed for anti-glioma drug delivery by active targeting the tumor. J. Eng. 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. 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 . Biotechnol. Mangadlao et al., Prostate-specific membrane antigen targeted gold nanoparticles for theranostics of prostate cancer. C 90, 589601 (2018), N.H. Levi-Polyachenko et al., Rapid photothermal intracellular drug delivery using multiwalled carbon nanotubes. 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Mater. Mater. Cancer 17, 20 (2016), B. Ruozi et al., PLGA nanoparticles loaded cerebrolysin: studies on their preparation and investigation of the effect of storage and serum stability with reference to traumatic brain injury. There is an exponential growth in the field of nano-based sensing and drug delivery [12,13,14,15,16,17,18,19,20]. World J Hepatol. Am. 2023 Mar 27;15(3):393-409. doi: 10.4254/wjh.v15.i3.393. Eur. PEG-PLGA nanoparticles were conjugated with AS1411, a DNA aptamer, that binds to a protein highly expressed in the plasma membrane of cancer and the endothelial cells of angiogenic blood vessels. Palazzolo S, Bayda S, Hadla M, Caligiuri I, Corona G, Toffoli G, Rizzolio F. Curr Med Chem. by V. Kumar, N. Dasgupta, S. Ranjan (CRC Press, Boca Raton, 2018), pp. The concept has been discussed in the active targeting section of this review. Front Mol Biosci. Biomater. Int. Release 261, 113125 (2017), X. Chen et al., Co-delivery of paclitaxel and anti-survivin siRNA via redox-sensitive oligopeptide liposomes for the synergistic treatment of breast cancer and metastasis. Another key issue is the challenge of regulatory approval of nanomedicines, as there are no specific guidelines set by FDA for the products with nanomaterials. Mock et al., Evidence for distinct mechanisms of uptake and antitumor activity of secretory phospholipase A2 responsive liposome in prostate cancer. Nanotechnology has led to several promising results with its applications in the diagnosis and treatment of cancer, including drug delivery [ 2 ], gene therapy, detection and diagnosis, drug carriage, biomarker mapping, targeted therapy, and molecular imaging. Adv. Terms and Conditions, Control. 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. Chem. The cytotoxicity of the dendrimer encapsulated doxorubicin and LFC131-DOX-D4 to BT-549-Luc cells was evaluated and the IC50 value of LFC131-DOXD4 was 2.8 fold of DOX-D4 against BT-549-Luc cells and it was 6.8 fold of DOX-D4 against T47D cells after 24h of incubation, indicating that the ligand conjugated doxorubicin encapsulated dendrimer can enhance the cytotoxicity of the drug against the cancer cell lines [281]. -. 2020 Aug 20;7:193. doi: 10.3389/fmolb.2020.00193. Int. 105, 228241 (2016), O. Akhavan et al., The use of a glucose-reduced graphene oxide suspension for photothermal cancer therapy. J. Nanosci. All these strategies can reduce the systemic toxicity at the tumor sites by ensuring that healthy cells are not affected. Cancer Lett. Additionally, since these nanocarriers interact with the biomolecules and may tend to aggregate forming a protein corona, disturbing the regular function of nanomedicine formulations and rendering them ineffective in controlling the cancer cell growth [286]. 13, 6769 (2018), S.V.K. Mater. Sci. Ind. It is well-known that the activity of the anticancer drugs is greatly attenuated by the time drug reaches the target, which can render the treatment to be ineffective and increase off-target effects. 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]. Med. have fabricated and characterized such dual ligandreceptor nanosystems using gold (Au) nanoparticles. Active targeting approach has been exploited to increase internalization of nanoparticles by the target cells and improve the drug delivery efficacy. Sci. Nanoparticles (1-100 nm) can be used to treat cancer due to their specific advantages such as biocompatibility, reduced toxicity, more excellent stability, enhanced permeability and retention effect, and precise targeting. 30(45), 299315 (2009), Y. Kato et al., Acidic extracellular microenvironment and cancer. Biomacromolecules 15(6), 19551969 (2014), N. Kamaly et al., Targeted polymeric therapeutic nanoparticles: design, development and clinical translation. Daima, Contemporary developments in nanobiotechnology: applications, toxicity, sustainability and future perspective, in Nanobiotechnology: human health and the environment, ed. The size and shape of nanomaterials determine the extent of their tumor accumulation and in vivo distribution. Natl. Kumar, F. Mohammad, Magnetic nanomaterials for hyperthermia-based therapy and controlled drug delivery. The biodistribution profile is also strongly influenced by active clearance processes posed by various immune cells, and blood flow/renal filtration rate. 17, 201209 (2015), A. Al Faraj, A.P. Colloids Surf. Moreover, for nanomaterials that do extravasate by crossing the vasculature, deeper penetration to tumor site is impeded by the interstitial tumor matrix. Likewise, Thanh et al., generated Heparin-functionalized monomethoxy PEG-polyamide amine dendrimer (HEP-mPEG) with effective encapsulation of DOX. C 82, 291298 (2018), C. Chittasupho, S. Anuchapreeda, N. Sarisuta, CXCR284 targeted dendrimer for anti-cancer drug delivery and breast cancer cell migration inhibition. Drug Deliv. Careers. Lu et al., Magnetic graphene oxide for dual targeted delivery of doxorubicin and photothermal therapy. Int. 22(27), 1377313781 (2012), Y. Wang et al., Graphene oxide covalently grafted upconversion nanoparticles for combined NIR mediated imaging and photothermal/photodynamic cancer therapy. Int. The in vivo transplantable liver tumor bearing BALB/c nude mice treated with docetaxel loaded Gal-pD-TPGS-PLA/NPs exhibited noticeable tumor growth inhibition when compared to other nanoformulations and free Taxotere. 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. Funct. Mater. Besides, liposomal co-delivery of chemotherapeutic agents can minimize cancer cell drug resistance and make them more sensitive to individual drugs. ACS Appl. This major setback has led to the development of ligand-directed liposomes for active targeting and treatment of different types of cancer. 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. Nat. Biomaterials 33(4), 11801189 (2012), Y. Qiu et al., Surface chemistry and aspect ratio mediated cellular uptake of Au nanorods. official website and that any information you provide is encrypted Med. The carbon spheres provided high drug loading capacity along with sustained release of drug under acidic pH, which is the normal tumor microenvironment. Release 141(3), 320327 (2010), X. Huang et al., The effect of the shape of mesoporous silica nanoparticles on cellular uptake and cell function. Spectrochim. Initially, we mention different forms of ovarian cancer biomarkers involving CA125, human epididymis protein 4 (HE4), mucin 1 (MUC1), and prostate. Nanotechnol. Drug Deliv. Rev. Sci. B Biol. 48(61), 76407642 (2012), R. 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Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Here, the size and size-dependent properties of the material will be the key to improving penetration into the matrix. In another study, iron oxide nanoparticles were used to deliver OVA, an anticancer vaccine. This heterogeneity adds another layer of complexity to passive targeting. J. Pharm. The critical aspect to this conjugation is to maintain the stability of the conjugated ligands during the adverse environment presented by the physiological environment, and various approaches have been undertaken to achieve it [32]. The results demonstrated that these iron oxide nanoparticles are effectively internalized by human prostate cancer cell line PC-3. Nanoconstructs for theranostic application in cancer: Challenges and strategies to enhance the delivery. Wong et al. Mol. 2018;68:394. doi: 10.3322/caac.21492. 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Gubernator, Active methods of drug loading into liposomes: recent strategies for stable drug entrapment and increased in vivo activity. Unfortunately, the understanding of EPR effects is limited by the unavailability of accurately recapitulated solid tumor models in humans. B Biointerfaces 169, 265272 (2018), A. Mohammadi Gazestani et al., In vivo evaluation of the combination effect of near-infrared laser and 5-fluorouracil-loaded PLGA-coated magnetite nanographene oxide. Nat. In one study, anti-HER2 targeting ligand moieties functionalized on the surface of liposome increased the cellular uptake of the nanoparticles in HER2-expressing cancer cells. government site. 7, 653 (2010), S.K. VR acknowledges the NIH (EB022641). In additionto functional groups on their branches, they are suitable for loading and binding diverse hydrophilic and hydrophobic drugs. Eng. Likewise, PEG capped Au nanoparticles coated with [Pt(1R,2R-diaminocyclohexane) (H2O)2]2NO3 were takenup, and localized in the lung epithelial and colon cancer cell lines showing more significant effects than the drug alone [128].

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