Nano-carriers such as liposomes, micelles, dendritic macromolecules, quantum dots, and carbon nanotubes have been widely used in cancer treatment. Epub 2014 Aug 9. By using this website, you agree to our Likewise, doxorubicin-loaded modified PEGylated liposomes were developed for targeted delivery of drug to hepatocellular carcinoma. Linear type of FC131 (LFC131) ligand conjugated, doxorubicin encapsulated polyamide amine dendrimer was developed using polyamide amine dendrimer generation 4.0 (D4). We further elaborate on the topical progress made to date toward nanomaterial engineering for cancer therapy, including current strategies for drug targeting and release for efficient cancer administration. 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]. 353(1), 2632 (2007), F. Zhao et al., Cellular uptake, intracellular trafficking, and cytotoxicity of nanomaterials. Byrne, T. Betancourt, L. Brannon-Peppas, Active targeting schemes for nanoparticle systems in cancer therapeutics. Offers up-to-date information on the target therapies used in cancer treatment. Nanomaterials used in cancer therapy can be classified into several main . C 96, 286294 (2019), D.D. Int. Int. 7(7), 1701143 (2017), Y. Wen, J.K. Oh, Intracellular delivery cellulose-based bionanogels with dual temperature/pH-response for cancer therapy. 24(48), 64336437 (2012), P. Shi et al., pH-responsive NIR enhanced drug release from gold nanocages possesses high potency against cancer cells. Lin, Effect of surface functionalization of MCM-41-type mesoporous silica nanoparticles on the endocytosis by human cancer cells. Mock et al., Evidence for distinct mechanisms of uptake and antitumor activity of secretory phospholipase A2 responsive liposome in prostate cancer. Rev. Nanotechnol. All samples were stained with 0.5% uranyl acetate for 1min. In the paradigm of nanomedicine, nanotechnology is being embraced to obtain effective drug delivery, establish novel in vitro diagnostics, and develop nano-based implants [7, 10, 11]. 3. The advent of nanotechnology has revolutionized . Eur. Mater. Colloids Surf. The use of nanocarriers in the treatment of cancer may result in unwanted toxicity through unfavourable interactions with biological entities [289]. Pharm. Rev. These particles can selectively target human osteosarcoma cells and are capable of pH-responsive antitumor drug delivery. Recent investigations on multi-walled carbon nanotubes (MWCNTs) for the co-delivery of drugs have revealed that the release of drug at the cancer site, and the uptake by the cells showed the potential for treating multi-drug resistant cancer [198]. Colloids Surf. Would you like email updates of new search results? Therefore, further advances in understanding tumor biology, understanding EPR effects in varieties of the tumor is essential. In vivo fluorescence imaging revealed the distribution of the drug in organs and these carbon nanospheres exercised antitumor effect in SCID mice bearing oesophageal tumors. Navya, H.K. Today Proc. Eng. Rev. 12(1), 320 (2018), S.-I. Most types of radiation used for cancer treatment utilize X-rays, gamma rays, and charged particles. 252(1), 263266 (2003), X. 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. Nanoparticle-Based Drug Delivery in Cancer Therapy and Its Role in Overcoming Drug Resistance. B 3(36), 71537172 (2015), R. Coradeghini et al., Size-dependent toxicity and cell interaction mechanisms of gold nanoparticles on mouse fibroblasts. The extent and kinetics of nanomaterial accumulation at the tumor site are influenced by their size. 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. However, the siRNA or temozolomide treatment mediated by the folate-targeted nanocarrier was able to prevent glioma growth, the combination therapy was more effective than the individual treatment [273]. 7b. Nanomaterial-based smart, targeted systems exploit the multivalent nature of interactions of ligands with the target antigens. 71(3), 14051414 (2015), Q. Pan et al., Lactobionic acid and carboxymethyl chitosan functionalized graphene oxide nanocomposites as targeted anticancer drug delivery systems. Release 172(3), 782794 (2013), C. Wong et al., Multistage nanoparticle delivery system for deep penetration into tumor tissue. Photobiol. Sci. J. Choi et al., Mechanism of active targeting in solid tumors with transferrin-containing gold nanoparticles. Eng. 9, 789 (2003), P.N. These liposomal formulations exhibited negative zeta potential values and an in vitro release study demonstrated that the liposomal formulations displayed good stability, and an extended circulation time required to avoid drug clearance before arrival at the target cells. Since there are a multitude of smaller interactions presented by diverse complex biomolecules based on simple van der Waals interactions, the cumulative effects of these smaller interactions can hinder nanoparticles approach to their target sites. Control. 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. 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]. Traditional cancer therapies include chemotherapy, radiation therapy, targeted therapy, and immunotherapy. J. Nanomed. Iran. Amongst the widely used strategies, today in cancer research is nanotechnology. Nanotechnology biomarker screening could be used to detect disease in a very small amount of cells or tissue. Interestingly, there was a significant tumor growth inhibition in the treatment group with doxorubicin-loaded lactoferrin-PLS of HepG2 tumors when compared to only doxorubicin-loaded PLS and free doxorubicin, with no significant change in the body weight observed as shown in Fig. 24, 86248631 (2018), D.C. Manatunga et al., Effective delivery of hydrophobic drugs to breast and liver cancer cells using a hybrid inorganic nanocarrier: a detailed investigation using cytotoxicity assays, fluorescence imaging and flow cytometry. Similarly, the PEGylated liposomes have been used in delivering celastrol, irinotecan, resveratrol in the treatment of breast cancer and glioblastoma [236, 237]. Biomaterials 33(3), 856866 (2012), A. Kumar et al., Gold nanoparticles functionalized with therapeutic and targeted peptides for cancer treatment. Biopharm. Additionally, mesoporous silica nanomaterials for the CD44-targeting pH responsive smart drug delivery system were developed by hyaluronic acid end-capping and loaded with doxorubicin. Drug Deliv. Redox activated polymeric nanoparticles in tumor therapy (Elsevier, Amsterdam, 2017). Also, these platforms can provide competent drug delivery systems responsive to various stimuli to enhance the therapeutic efficacy and reduce the side effects of loaded drugs. Interfaces 7(32), 1817918187 (2015), L. Xiong et al., Cancer-cell-specific nuclear-targeted drug delivery by dual-ligand-modified mesoporous silica nanoparticles. Mol. Eng. 13, 34673480 (2018), J. Guo et al., Aptamer-functionalized PEGPLGA nanoparticles for enhanced anti-glioma drug delivery. A comprehensive set of guidelines for regulatory approval is urgently needed to expedite the evaluation and approval of cancer nanotherapeutics. Thanh et al., Low systemic toxicity nanocarriers fabricated from heparin-mPEG and PAMAM dendrimers for controlled drug release. Further, HKD appreciates the Centre for Advanced Materials and Industrial Chemistry (CAMIC) in the School of Sciences, RMIT University, Australia for an Honorary Visiting Research Fellowship. Control. Cancer is a disease with complex pathological process. Targeted therapy using theranostic IGF1-iron oxide nanoparticles-doxorubicin significantly inhibited the growth of pancreatic PDX tumors showing potential for improved therapeutic outcomes as shown in Fig. Interfaces 10, 2116021172 (2018), N. Guldris et al., Orthogonal clickable iron oxide nanoparticle platform for targeting, imaging, and on-demand release. Chem. Biomaterials 30(5), 859866 (2009), Y.-I. The tumor volume as depicted in Fig. Adv. 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. Sci. J. Cancer 17(1), 20 (2017), J.E. 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 scale bars are 100m. Sci. Nanotechnology-based delivery systems hold the potential to overcome such limitations. Acad. B Appl. 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. Colloids Surf. Int. Yao Y, Zhou Y, Liu L, Xu Y, Chen Q, Wang Y, Wu S, Deng Y, Zhang J, Shao A. J. Photochem. 34, 7000 (2016), V.P. 17(8), 1600457 (2017), K. Jain et al., Dendrimer toxicity: lets meet the challenge. Sci. Nanotechnol. A schematic representation of the major challenges in the delivery of cancer nanotherapeutics is depicted in Fig. Chem. 65, 393404 (2018), H.K. Int. 23(11), 14181423 (2005), D. Peer et al., Nanocarriers as an emerging platform for cancer therapy. Mater. Upon intravenous administration of nanoparticles into patient-derived xenograft (PDX) prototype of pancreatic cancer, exceptional tumor targeting and penetration was obtained. 151, 812820 (2016), J. Chen et al., One-step reduction and PEGylation of graphene oxide for photothermally controlled drug delivery. Expert Rev Mol Diagn. Nat. The ensuing section discusses major physicochemical properties of nanomaterials and their design considerations for therapeutic and diagnostic applications. Please enable it to take advantage of the complete set of features! Over the past 20years, commendable progress has been made in biomedical applications of liposomes improving the therapeutic index of the encapsulated drugs. 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. Macromol. Rotello, Surface recognition of biomacromolecules using nanoparticle receptors. J. Pharm. -. 108, 565573 (2018), A.M. Nassir et al., Resveratrol-loaded PLGA nanoparticles mediated programmed cell death in prostate cancer cells. 41(7), 29713010 (2012), D. Zhu et al., Docetaxel (DTX)-loaded polydopamine-modified TPGS-PLA nanoparticles as a targeted drug delivery system for the treatment of liver cancer. 122, 311330 (2018), H.K. Sci. Mater. 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]. Carbon 107, 8799 (2016), Q. Zhang et al., Biocompatible, uniform, and redispersible mesoporous silica nanoparticles for cancer-targeted drug delivery in vivo. 22(27), 1377313781 (2012), Y. Wang et al., Graphene oxide covalently grafted upconversion nanoparticles for combined NIR mediated imaging and photothermal/photodynamic cancer therapy. Sci. Colloids Surf. In one of the recent reports the drug release and stability of pH-sensitive Au nanoparticles loaded with 5-fluorouracil capped with cetyltrimethylammonium bromide (CTAB) was achieved by incorporating into gel and cream bases [142]. Recently, PLGA [poly(lactic-co-glycolic acid)] based nanomaterials have been developed, demonstrating that suitable surface coating of the nanomaterials provides extended circulation time. Chem. Therefore, it is essential to improve new procedures for the diagnosis and treatment of BC. 24(40), 54765480 (2012), Z.J. 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. This is known as enhanced permeability and retention (EPR) effect, which is the basis of passive targeting [31]. Farooq et al., Gold nanoparticles-enabled efficient dual delivery of anticancer therapeutics to HeLa cells. Mater. All the authors have made substantial intellectual contribution in the preparation of the manuscript. From the above discussion, it can be concluded that nanomaterials for therapeutic applications need to be engineered carefully with respect to their size and shape, because both of them have noteworthy impact on the uptake process of cells, and can potentially induce cellular responses. In another study, Zhou et al. National Library of Medicine In another study, resveratrol encapsulated PLGA [poly(lactic-co-glycolic acid)] nanoparticles have been constructed for prostate cancer therapy. J. Photochem. C 89, 307315 (2018), C. Huang et al., Amphiphilic prodrug-decorated graphene oxide as a multi-functional drug delivery system for efficient cancer therapy. 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]. Soc. The designed nanoformulation was spherical in shape with 15654nm size and a negative zeta potential exhibiting increased cytotoxicity in C6 glioma cells. Phytochemical-based nanodrugs going beyond the state-of-the-art in cancer management-Targeting cancer stem cells in the framework of predictive, preventive, personalized medicine. 45(6), 10821091 (2017), Z. Muhammad et al., PEG capped methotrexate silver nanoparticles for efficient anticancer activity and biocompatibility. The cellular entry of nanomaterials depends on surface charge [109]. Various ligands such as antibodies, proteins, peptides, aptamers and small molecules have been used to target specific cells [268]. J. Nanomed. Therapeutic efficacy of passive targeted approaches is limited by the heterogeneity of the EPR effects seen within and between different tumors. Eur. 16(4), 12731304 (2017), Y. Chi et al., Redox-sensitive and hyaluronic acid functionalized liposomes for cytoplasmic drug delivery to osteosarcoma in animal models. Mater. Often in the breast cancer cells, Mucin 1 (MUC1), a cell surface protein, will be overexpressed. Natl. J. Nanomed. Alongside, case-by-case basis investigations are required to harness the tremendous potential of cancer nanotherapeutics. 6(4), 662668 (2006), P. Decuzzi et al., Size and shape effects in the biodistribution of intravascularly injected particles. Emerging evidence has also shown that nanoparticles have the . Daima, Contemporary developments in nanobiotechnology: applications, toxicity, sustainability and future perspective, in Nanobiotechnology: human health and the environment, ed. Dalton Trans. 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. In conjunction to physicochemical properties, the nanomaterial storage and stability may also have an influence on their pharmacological performance [287, 288]. Effect of OVA-iron oxide nanoparticles: macrophages activation with different concentrations of OVA, and production of a TNF-, b IL-6, c IFN-. Moreover, for nanomaterials that do extravasate by crossing the vasculature, deeper penetration to tumor site is impeded by the interstitial tumor matrix. Clin. Nat. Sci. have demonstrated that the internalization of magnetic nanoparticles inside HeLa cells is dependent on the nanoparticle surface charge and incubation time. J. Biomed. 217(3), 205216 (2013), Z. Ji et al., Designed synthesis of CeO2 nanorods and nanowires for studying toxicological effects of high aspect ratio nanomaterials. Eur. They observed that this dual targeting system is more efficient in delivering Au nanoparticles to cancer cells than their corresponding single ligand system [54]. Biomaterials 33(4), 11801189 (2012), Y. Qiu et al., Surface chemistry and aspect ratio mediated cellular uptake of Au nanorods. Nanoscale 7(22), 1007110077 (2015), Y. Su et al., Redox-responsive polymerdrug conjugates based on doxorubicin and chitosan oligosaccharide-g-stearic acid for cancer therapy. Soc. 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. Pharmacother. It could also highlight a tumor's parameters and margins to enhance the precision of diagnostics. 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. Mol. Biomed. Therefore, polymeric nanoparticles can be effectively used to deliver cancer therapeutics by active and passive targeting. Nanomed. Evol. Sci. Nat. 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. 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. Artif. Cells were incubated for 48h and BCL-2 siRNA concentration used is 20nM (c); Mean tumor volume determined using magnetic resonance imaging measured after 25days of the first injection. The active targeting was achieved using cetuximab, an epidermal growth factor receptor (EGFR) monoclonal antibody, since epidermal growth factor receptor is highly expressed on the tumor surface of colorectal cancer cells. Du et al., Hyaluronic acid-functionalized half-generation of sectorial dendrimers for anticancer drug delivery and enhanced biocompatibility. Chung et al., The effect of surface functionalization of PLGA nanoparticles by heparin- or chitosan-conjugated Pluronic on tumor targeting. Nanoscale 6(2), 758765 (2014), H.K. 8(3), 602616 (2018), M. Wei et al., Lactoferrin-modified PEGylated liposomes loaded with doxorubicin for targeting delivery to hepatocellular carcinoma.