Despite the numerous advantages of the nano-based cancer therapeutics, clinical translation of these nanomedicines remains to be a challenging mission. Du et al., Hyaluronic acid-functionalized half-generation of sectorial dendrimers for anticancer drug delivery and enhanced biocompatibility. 2023 Mar 11;15(6):1400. doi: 10.3390/polym15061400. Nanotechnology has recently sparked an interest in a variety of areas, including medicine, chemistry, physics, and biology. 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]. The effectiveness of anticancer drug treatment can be achieved only when the administered drug is of proper dosage and display maximal activity in the cancer cells. ACS Nano 9(8), 79767991 (2015), C.S. Adv. ACS Appl. Polymeric nanoparticles serve as a versatile platform to deliver drugs due to their different chemical composition, charge and physical structure. 108, 565573 (2018), A.M. Nassir et al., Resveratrol-loaded PLGA nanoparticles mediated programmed cell death in prostate cancer cells. 119, 310321 (2017), K. ztrk et al., Effective targeting of gemcitabine to pancreatic cancer through PEG-cored Flt-1 antibody-conjugated dendrimers. The possibility of using mesoporous silica nanomaterials as potential nanocarriers has driven interest in many biomedical applications. Further, antibodies, small proteins, peptides, nucleic acid-based ligands, aptamers, small molecules, and oligosaccharides are used as targeting ligands [134,135,136,137,138,139]. In this context, many studies have demonstrated that cellular interactions of polymer-based nanomaterials are highly influenced by their surface chemistry [120,121,122]. Biomacromolecules 14(8), 26012610 (2013), A. 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In spite of widespread research and the preclinical development of liposomal formulations from several decades, only a few liposomal drug formulations have been approved by the FDA for clinical use [246]. Macromol. Proc. Control. Acad. Amongst the widely used strategies, today in cancer research is nanotechnology. 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. Biotechnol. 10, 36633685 (2015), A.A. Bhirde et al., Distribution and clearance of PEG-single-walled carbon nanotube cancer drug delivery vehicles in mice. Nat. Bhattacharyya et al. 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. 133(44), 1756017563 (2011), Y.Y. These surface modifiable mesoporous silica nanomaterials have been exploited to deliver curcumin to breast cancer cell lines that were loaded with hyaluronan or polyethyleneimine-folic acid and were tested on mouse xenograft model [221]. 46(43), 1483114838 (2017), N. Li et al., Curcumin-loaded redox-responsive mesoporous silica nanoparticles for targeted breast cancer therapy. Iacobazzi et al., Targeting human liver cancer cells with lactobionic acid-G(4)-PAMAM-FITC sorafenib loaded dendrimers. Biotechnol. 26(6), 876885 (2018), S. Nicolas et al., Polymeric nanocapsules as drug carriers for sustained anticancer activity of calcitriol in breast cancer cells. 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. ACS Bio Med Chem Au. Med. Likewise, intracellular drug delivery can be enhanced by utilizing carbon nanotube-based phototherapies. However, some cons have also been noticed due to which the use of nanotechnology at a larger scale is not being encouraged. 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. In passive targeting, the nanocarriers pass through the leaky walls and accumulate at the tumor site by the enhanced permeability and retention (EPR) effect. 353(1), 2632 (2007), F. Zhao et al., Cellular uptake, intracellular trafficking, and cytotoxicity of nanomaterials. Cancer; Cellular targeting; Chemotherapy; Cryosurgery; Multidrug resistance; Nanoparticles; Scale-up. 2 [29]. Nanoparticles (NP) have been used in tumor therapies as appropriate tools for enhancing drug delivery efficacy and enabling . Chem. 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Werner et al., Folate-targeted nanoparticle delivery of chemo- and radiotherapeutics for the treatment of ovarian cancer peritoneal metastasis. Bioconjug. Several researchers have demonstrated that half-generation dendrimers exhibit lower toxicity than the full generation of polyamide amine [277,278,279]. National Library of Medicine 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]. Photobiol. B 2(5), 452470 (2014), H. Alimoradi, et al., in Nanostructures for drug delivery. Furthermore, silicon-based nanoparticles with quasi-hemispherical, discoidal and cylindrical shapes were used to study the effect of shape-dependent distribution, with discoidal particles distributed to most of the organs tested as compared to other shapes that had less diverse biodistributions [107]. Schematic illustration representing various challenges involved in the delivery of cancer nanotherapeutics. A multi-functional graphene oxide based drug delivery system could target cancerous tissues, and exhibit antitumor effect with no systemic toxicity in B16 tumor-bearing mice [212]. a The effect of IGF1R in MIAPaCa-2 cells was assessed by immunofluorescence labeling employing an anti-IGF1R antibody (shown in red color). These nanoformulations showed better biocompatibility with low toxicity and inhibited tumor growth to a greater extent than curcumin alone. Nanotechnol. mRNA transcriptome profiling of human hepatocellular carcinoma cells HepG2 treated with. Other major nanomaterials that have noticeable contribution in drug delivery are carbon-based nanostructures and mesoporous silica nanoparticles. 65, 393404 (2018), H.K. Release 141(3), 320327 (2010), X. Huang et al., The effect of the shape of mesoporous silica nanoparticles on cellular uptake and cell function. All these strategies can reduce the systemic toxicity at the tumor sites by ensuring that healthy cells are not affected. Nanotechnol. Offers up-to-date information on the target therapies used in cancer treatment. Colloids Surf. Nat. https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts Wu S, Zhu W, Thompson P, Hannun YA. Daima, Rational engineering of physicochemical properties of nanomaterials for biomedical applications with nanotoxicological perspectives. PLoS ONE 12(8), e0181944e0181944 (2017), R.M. J. Pharm. 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. Release 200, 138157 (2015), C.K. Smart Magnetic Drug Delivery Systems for the Treatment of Cancer. Mater. NanoBiotechnology 3(1), 4045 (2007), A. Verma, V.M. Biomater. 24(48), 64336437 (2012), P. Shi et al., pH-responsive NIR enhanced drug release from gold nanocages possesses high potency against cancer cells. Biomater. Epub 2020 Oct 16. Therefore, polymeric nanoparticles can be effectively used to deliver cancer therapeutics by active and passive targeting. PMC Cells Nanomed. A pH sensitive nanoplatform can generate heat, following light absorption upon irradiation with near-IR (NIR) light and due to the toxicity of DOX, offering a potential multimodal nanomedicine for efficient cancer treatment [199]. 1. Due to the lack of understanding of toxicity and in vivo behaviour of nanoformulations, clinical trials are experiencing major setbacks. Cancer is one of the leading causes of death and morbidity with a complex pathophysiology. Chem. Iran. 11, 66936702 (2016), S.A. Sadat Shandiz et al., Novel imatinib-loaded silver nanoparticles for enhanced apoptosis of human breast cancer MCF-7 cells. Front. Rotello, Functionalized gold nanoparticles for drug delivery. 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.
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