Also, difficulties in the approval will tend to increase due to the development of multifunctional nanoplatforms. 13, 24052426 (2018), B. Xiao et al., Co-delivery of camptothecin and curcumin by cationic polymeric nanoparticles for synergistic colon cancer combination chemotherapy. In the fight against cancer, early detection is a key factor for successful treatment. People will never need to disrupt or obliterate the environment since they can use unused things and left over things that have been used up already. Soc. The designed nanoformulation was spherical in shape with 15654nm size and a negative zeta potential exhibiting increased cytotoxicity in C6 glioma cells. 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. Understanding the complications involved in cancer cell physiology and the tumor microenvironment, along with drug and carrier pharmacokinetics is essential for the development of successful new cancer therapeutics. They have developed gelatin particles, 100nm in diameter, which upon extravasation into tumor tissue reduce in size to 10nm, through degradation by tumor-associated matrix metalloproteinases [39]. Similarly, the PEGylated liposomes have been used in delivering celastrol, irinotecan, resveratrol in the treatment of breast cancer and glioblastoma [236, 237]. These nanoparticles exhibited a significant decrease in cell viability and greater cytotoxicity toward LNCaP cells when compared to free resveratrol. 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. Nanotechnology-based delivery systems hold the potential to overcome such limitations. 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. Sci. Fan et al., Thermoresponsive supramolecular chemotherapy by V-shaped armed -cyclodextrin star polymer to overcome drug resistance. Drug packaging efficacy depends on encapsulation or drug conjugation efficiency. J. Pharm. Natl. C 89, 1524 (2018), P. Li et al., Lanthanide-doped upconversion nanoparticles complexed with nano-oxide graphene used for upconversion fluorescence imaging and photothermal therapy. 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]. Nat. Biomaterials 32(13), 34353446 (2011), O. Harush-Frenkel et al., Targeting of nanoparticles to the clathrin-mediated endocytic pathway. 46, 2533 (2018), Z. Wei et al., Antitumor effect of a Pt-loaded nanocomposite based on graphene quantum dots combats hypoxia-induced chemoresistance of oral squamous cell carcinoma. Chem. The results demonstrated that the high drug loading capacity and less systemic toxicity of G4.0 polyamide amine-HEP-mPEG/DOX could serve as a suitable drug delivery system [280]. 13, 1113 (2018), M.B. Eng. Better diagnostics. sharing sensitive information, make sure youre on a federal ACS Nano 12(4), 37143725 (2018), M.A. Recently, Peng et al. The tumor volume as depicted in Fig. 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. Polymeric nanoparticles serve as a versatile platform to deliver drugs due to their different chemical composition, charge and physical structure. 2023 Apr 4;28(1):28. doi: 10.1186/s11658-023-00442-z. eCollection 2020. In this context, Li et al., have developed novel nanocarrier systems for tumor targeting and precise release of curcumin. 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]. 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]. Please enable it to take advantage of the complete set of features! Therefore, Nanotoxicology a branch of nanomedicine has emerged as an essential field of research, paving the way for the assessment of toxicity of nanoparticles. Nat. They employed EGFR and folate receptor (FR) overexpressed in ovarian cancer as target surface molecules, and used monoclonal antibodies against these receptors as dual ligands for Au nanoparticle targeting. J. Pharm. 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. In addition, many other factors have a profound consequence on nanomaterials uptake and distribution in cells. We also discuss the current challenges and perspectives of nanomaterials in effective cancer management. Active targeting approach has been exploited to increase internalization of nanoparticles by the target cells and improve the drug delivery efficacy. Int. There are different classes of liposomes used as drug delivery platforms for enhancing the efficacy of cancer therapeutics [232]. Formulations have been approved for the treatment of Kaposis sarcoma, acute lymphoblastic leukemia, pancreatic cancer, ovarian cancer, multiple myeloma and metastatic breast cancer including Doxil, Myocet, DaunoXome, DepoCyte, Lipoplatin. As illustrated in Fig. Several studies have revealed the detrimental properties of nanocarriers due to their toxicity [290, 291]. 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. Disclaimer. Recently, Wan et al. 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. 13, 6769 (2018), S.V.K. The outcomes of the study are promising and recommend a topical nanoformulation to enhance drug efficacy against skin cancer. In open-loop control systems, external factors such as magnetic pulses, thermal, acoustic pulses or electric fields control drug release. The biodistribution profile is also strongly influenced by active clearance processes posed by various immune cells, and blood flow/renal filtration rate. 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. Mater. Active targeting, also known as the ligand-mediated targeted approach, involves affinity based recognition, retention and facilitated uptake by the targeted cells (Fig. J. Pharm. Additionally, the in vivo biodistribution of nanoparticles suggest that the negatively charged particles accumulate in tumor sites more efficiently [110]. Nano Lett. Ohno et al., Systemically injected exosomes targeted to EGFR deliver antitumor microRNA to breast cancer cells. Natl. VR acknowledges the NIH (EB022641). Further, as illustrated in Fig. In another study, ultrasmall Au nanoparticles of sizes ranging from 2 to 15nm coated with tiopronin were evaluated for their localization and penetration into breast cancer cells, and it was found that accumulation of smaller nanoparticles was higher in tumor tissues in mice [104]. Int. Acta Biomater. Polymeric nanoparticles are efficient in enhancing therapeutic and diagnostic effects over conventional medicines. Control. AK acknowledges International Max Planck Research School (IMPRS) Fellowship (Molecular Biology) from the Max Planck Society, Germany (2016-18) and Melbourne Research Scholarship for the support of his research at the University of Melbourne. Before 95(8), 46074612 (1998), G.-H. Int. These nanocarriers help overcome the unwanted side effects in normal tissues and increase circulation time, bioavailability, and accumulation of drug at target-site by reducing toxicity and protect the chemotherapeutic agents from the surrounding environment. Mater. Rev. 58, 349364 (2017), Y. Peng et al., Codelivery of temozolomide and siRNA with polymeric nanocarrier for effective glioma treatment. 2020 Aug 20;7:193. doi: 10.3389/fmolb.2020.00193. Mishra S, Bhatt T, Kumar H, Jain R, Shilpi S, Jain V. Front Pharmacol. ACS Nano 1(1), 5056 (2007), R.P. Smart Magnetic Drug Delivery Systems for the Treatment of Cancer. Cell Biochem. Carbon nanotubes can assist as drug delivery systems for effective targeting to cancer cells. In this context, many studies have demonstrated that cellular interactions of polymer-based nanomaterials are highly influenced by their surface chemistry [120,121,122]. J. As cancer is known to be a consequence of DNA defects, many countries are battling with nipping it in the bud, particularly developing nations [41]. ACS Nano 3(2), 307316 (2009), S.R. J. Mol. Biotechnol. 2019 Dec;33(6):1071-1093. doi: 10.1016/j.hoc.2019.08.002. J. Photochem. ACS Nano 10(4), 44104420 (2016), Y. Qin et al., Near-infrared light remote-controlled intracellular anti-cancer drug delivery using thermo/pH sensitive nanovehicle. 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. Int. See this image and copyright information in PMC. 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. Health B 14(8), 593632 (2011), H. Maeda, H. Nakamura, J. Fang, The EPR effect for macromolecular drug delivery to solid tumors: improvement of tumor uptake, lowering of systemic toxicity, and distinct tumor imaging in vivo. The large-scale production of nanoformulations, however, is quite challenging as their physicochemical properties may vary from batch to batch. Ed. Biopharm. 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]. B Appl. Nano-Bio Interfacial Research Laboratory (NBIRL), Department of Biotechnology, Siddaganga Institute of Technology, Tumkur, Karnataka, 572103, India, Melbourne Integrative Genomics, School of BioSciences/School of Mathematics and Statistics, The University of Melbourne, Melbourne, VIC, 3010, Australia, School of Optometry, Indiana University, Bloomington, Indiana, 47405, USA, Centre for Advanced Materials and Industrial Chemistry, School of Science, RMIT University, Melbourne, VIC, 3001, Australia, Suresh Kumar Bhargava&Hemant Kumar Daima, Department of Chemistry, University of Massachusetts (UMass) Amherst, 710 North Pleasant Street, Amherst, MA, 01003, USA, Amity Institute of Biotechnology, Amity University Rajasthan, Kant Kalwar, NH-11C, Jaipur-Delhi Highway, Jaipur, Rajasthan, 303002, India, Department of Biotechnology, Bannari Amman Institute of Technology, Sathyamangalam, Erode, Tamil Nadu, 638401, India, You can also search for this author in Unauthorized use of these marks is strictly prohibited. Appl. Nanotechnology has the potential to circumvent several drawbacks of conventional therapeutic formulations. Daima et al., Complexation of plasmid DNA and poly(ethylene oxide)/poly(propylene oxide) polymers for safe gene delivery. 3(11), 779793 (2010), K. Yang, L. Feng, Z. Liu, Stimuli responsive drug delivery systems based on nano-graphene for cancer therapy. Mater. Release 172(3), 852861 (2013), S.K. 2020 Dec 15;591:119986. doi: 10.1016/j.ijpharm.2020.119986. 12, 77637776 (2017), Y. Li et al., Polyethylenimine-functionalized silver nanoparticle-based co-delivery of paclitaxel to induce HepG2 cell apoptosis. Soc. The table illustrates the type of inorganic nanomaterial used as nanocarrier, the explicit drug loaded on the carrier and the cancer cells. Carbon 107, 8799 (2016), Q. Zhang et al., Biocompatible, uniform, and redispersible mesoporous silica nanoparticles for cancer-targeted drug delivery in vivo. Interfaces 8(42), 2846828479 (2016), Y. Wang et al., An overview of nanotoxicity and nanomedicine research: principles, progress and implications for cancer therapy. In another study, Zhou et al. Kim et al., Co-eradication of breast cancer cells and cancer stem cells by cross-linked multilamellar liposomes enhances tumor treatment. Chem. 2017;37:1. W. 2015. Nanotechnology 20(11), 115103 (2009), J.-Z. Med. 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. Likewise, Thanh et al., generated Heparin-functionalized monomethoxy PEG-polyamide amine dendrimer (HEP-mPEG) with effective encapsulation of DOX. The structure of liposomes can be engineered to encapsulate the hydrophobic or hydrophilic drugs, or other small molecules, in the lipid bilayer or aqueous core, respectively [230]. J. Photochem. Biomater. Dalton Trans. Thus, it is imperative to develop effective formulations that can address the above cited challenges and provide selective targeting of tumor sites without significant damage to the viability of healthy tissues [3,4,5,6,7,8,9]. Acta Biomater. Biotechnol. C 90, 589601 (2018), N.H. Levi-Polyachenko et al., Rapid photothermal intracellular drug delivery using multiwalled carbon nanotubes. Biochem. The authors announce no competing of interest. 46(43), 1483114838 (2017), N. Li et al., Curcumin-loaded redox-responsive mesoporous silica nanoparticles for targeted breast cancer therapy. J. J. Pharm. Int. Wang et al., developed a multi-walled carbon nanotube platform with improved circulation half-life, and active targeting ability with high drug loading ratio. Mater. Howlader N, Noone AM, Krapcho M, Garshell J, Neyman N, Altekruse SF, Cronin KA, Howlander N, Aminou R. Waldron. These nanocarriers have demonstrated to decrease non-specific toxicities, improve drug delivery profiles, enhance drug stability and bioavailability, targeted drug delivery. Accessibility Endoplasmic retention is only one of the mechanisms describing tumor biology. Biomater. Comparative value of these approaches depends . Several strategies have also been developed to accomplish liposomal codelivery of chemotherapeutic agents. In another study, iron oxide nanoparticles were used to deliver OVA, an anticancer vaccine. Daima et al., Fine-tuning the antimicrobial profile of biocompatible gold nanoparticles by sequential surface functionalization using polyoxometalates and lysine. Nanotechnology is expected to be promising in many fields of medical applications, mainly in cancer treatment. 107(11), 29022913 (2018), L. Wang et al., A novel -enolase-targeted drug delivery system for high efficacy prostate cancer therapy. 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]. (n.d.). 3, 303312 (2005), Q. Liu et al., Differentiation of cancer cell type and phenotype using quantum dot-gold nanoparticle sensor arrays. Colloids Surf. The fabricated nanoparticles enhanced cellular uptake via CD44 receptor-mediated endocytosis by HeLa cells. 133(44), 1756017563 (2011), Y.Y. Accessibility J. Biomed. Recently, coreshell nanoparticles were also developed with a magnetic core and mesoporous silica nanomaterials shell to effectively deliver epirubicin. 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. Spectrochim. 26(6), 876885 (2018), S. Nicolas et al., Polymeric nanocapsules as drug carriers for sustained anticancer activity of calcitriol in breast cancer cells. Nat. Chem. J. Photochem. J. 520(1), 126138 (2017), C.T. 34, 7000 (2016), V.P. Effect of OVA-iron oxide nanoparticles: macrophages activation with different concentrations of OVA, and production of a TNF-, b IL-6, c IFN-. In the quest to get viable treatments with no. Classification of NP synthesis a top-down and b bottom-up approaches, Pictorial representation of active cellular, Pictorial representation of active cellular targeting, Various types of nanomaterials used in cancer therapy, Diagrammatic representation of NPs in cryosurgery, MeSH However, most of the research is limited to in vivo and in vitro studies, and the number of approved nanodrugs has not much amplified over the years. Mol. 107, 11501158 (2019), W. Zheng et al., Encapsulation of verapamil and doxorubicin by MPEG-PLA to reverse drug resistance in ovarian cancer. Natl. 171, 133138 (2017), A.A. Bhirde et al., Targeted killing of cancer cells in vivo and in vitro with EGF-directed carbon nanotube-based drug delivery. The size of the nanomaterials also influences the uptake of the drug by the cells and interactions with specific tissues for therapeutic purposes. Soc. Pharm. Res. Persistent insoluble particles in in the environment can have far bigger negative effects than those revealed by human health assessments. 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. Eng. Control. According to the World Health Organization, cancer is the second leading cause of death worldwide, accounting for 9.6 million deaths in 2018 [].The global efforts in cancer prevention, early diagnosis, screening and treatment, have been challenged by the complexity and variability of tumors (reviewed in []).The genomic instability of tumor cells and a pro-inflammatory . Colloids Surf. Areas covered: Nanoparticles (NPs) used as drug delivery vehicles consist of. 13(8), 24952505 (2017), Q. Liu et al., Facile synthesis by a covalent binding reaction for pH-responsive drug release of carboxylated chitosan coated hollow mesoporous silica nanoparticles. Table1 presents different nanocarriers loaded with drugs that are released to tumor sites based on specific stimuli. The nanoformulation exhibited a high rate of apoptosis against human liver cells and stronger anti-angiogenic effects together with inhibition of proliferation, migration, invasion, and tube formation [272]. 12, 67876797 (2017), S.-B. 11, 31593166 (2016), P.-C. Liang et al., Doxorubicin-modified magnetic nanoparticles as a drug delivery system for magnetic resonance imaging-monitoring magnet-enhancing tumor chemotherapy. Mater. The in vitro cytotoxicity studies revealed that doxorubicin formulations had increased antiproliferative effect and was time and dose-dependent as depicted in Fig. Several researchers have demonstrated that half-generation dendrimers exhibit lower toxicity than the full generation of polyamide amine [277,278,279]. 2018;9(1):3490. doi: 10.1038/s41467-018-05467-z. Biomaterials 32(10), 25402545 (2011), S. Bhattacharyya et al., Efficient delivery of gold nanoparticles by dual receptor targeting. 11(2), 140152 (2017), Article Biomol. This concentration difference on the cell surface is the basis for studies targeting cancer cells overexpressing EGFR [51, 52]. Discusses the limitations of target therapy for some cancer patients. In addition to tailoring the surface corona, engineered nanomaterials reduce their toxicity and enhance their stability [23, 44, 119]. 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/. Int. Int. It is anticipated that multiple drugs when delivered simultaneously to a cancer cell will exhibit a synergistic effect, when administered in an optimized ratio. Additionally, the size and shape of the nanomaterials impact the drug loading and release, along with the stability [102]. 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. Therefore, polymeric nanoparticles can be effectively used to deliver cancer therapeutics by active and passive targeting. The combination of chemotherapy with photothermal therapy has proved to be efficient when magnetic graphene oxide modified with PEG and cetuximab was used against CT-26 murine colorectal cells [214]. Oncotarget 8(35), 5873858753 (2017), L. Meng et al., Chitosan-based nanocarriers with pH and light dual response for anticancer drug delivery. Brito C, Loureno C, Magalhes J, Reis S, Borges M. Vaccines (Basel). C 91, 395403 (2018), G. Arya, M. Das, S.K. Sahoo, Evaluation of curcumin loaded chitosan/PEG blended PLGA nanoparticles for effective treatment of pancreatic cancer. have demonstrated increased cell membrane permeability by hyperthermia from multi-walled carbon nanotube, thereby enhancing drug delivery to tumor targets [201]. 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]. 1. The study has shown the sustained and pH-dependent release, in which the volume of the tumor reduced compared tothe untreated control. J. Am. However, some cons have also been noticed due to which the use of nanotechnology at a larger scale is not being encouraged. J. The in vitro studies discovered that the nanoparticledrug conjugate was more efficient in killing PMSA-expressing cells. Rotello, Functionalized gold nanoparticles for drug delivery. Tamoxifen and imatinib mesylate were released in controlled manner from the temperature sensitive liposomes prepared using a combination of phospholipids with a transition temperature near to 39C. 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. The review is based on the published data and sources of data upon which conclusions have been drawn can be found in the reference list. Provided by the Springer Nature SharedIt content-sharing initiative. Nanoparticles in precision medicine for ovarian cancer: From chemotherapy to immunotherapy. Pharm. ACS Appl. Chan, Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells. Acad. 3(1), 1 (2016), A. Wicki et al., Nanomedicine in cancer therapy: challenges, opportunities, and clinical applications. Today Proc. Blood-based liquid biopsy: insights into early detection, prediction, and treatment monitoring of bladder cancer. These nanocarriers were stable and their release was reported to be pH responsive. 129(32), 98569857 (2007), G. Han, P. Ghosh, V.M. Recent studies have demonstrated that size and shape of the gold (Au) nanoparticles influence thetransfection efficiency of small interfering RNA (siRNA). 2023 Mar 27;15(3):393-409. doi: 10.4254/wjh.v15.i3.393. 18(3), 15341541 (2018), X. Zhao et al., PEGylated multi-walled carbon nanotubes as versatile vector for tumor-specific intracellular triggered release with enhanced anti-cancer efficiency: optimization of length and PEGylation degree.
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