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Cited by 367Nanoparticle-Based Drug DeliveryNanoplatforms for cancer theranosticsDrug Transport and Resistance Mechanisms

The DOI matches its Crossref record; 219 of the 220 references it cites were found in a registry or an index.

Nanoparticle-Mediated Combination Therapy: Two-in-One Approach for Cancer

Open access
Gurunathan, Sangiliyandi, Kang, Min-Hee, Qasim, Muhammad, Kim, Jin-Hoi·2018·International Journal of Molecular Sciences
DOI 10.3390/ijms19103264PMC PMC6214025
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Abstract

Cancer represents a group of heterogeneous diseases characterized by uncontrolled growth and spread of abnormal cells, ultimately leading to death. Nanomedicine plays a significant role in the development of nanodrugs, nanodevices, drug delivery systems and nanocarriers. Some of the major issues in the treatment of cancer are multidrug resistance (MDR), narrow therapeutic window and undesired side effects of available anticancer drugs and the limitations of anticancer drugs. Several nanosystems being utilized for detection, diagnosis and treatment such as theranostic carriers, liposomes, carbon nanotubes, quantum dots, polymeric micelles, dendrimers and metallic nanoparticles. However, nonbiodegradable nanoparticles causes high tissue accumulation and leads to toxicity. MDR is considered a major impediment to cancer treatment due to metastatic tumors that develop resistance to chemotherapy. MDR contributes to the failure of chemotherapies in various cancers, including breast, ovarian, lung, gastrointestinal and hematological malignancies. Moreover, the therapeutic efficiency of anticancer drugs or nanoparticles (NPs) used alone is less than that of the combination of NPs and anticancer drugs. Combination therapy has long been adopted as the standard first-line treatment of several malignancies to improve the clinical outcome. Combination therapy with anticancer drugs has been shown to generally induce synergistic drug actions and deter the onset of drug resistance. Therefore, this review is designed to report and analyze the recent progress made to address combination therapy using NPs and anticancer drugs. We first provide a comprehensive overview of the angiogenesis and of the different types of NPs currently used in treatments of cancer; those emphasized in this review are liposomes, polymeric NPs, polymeric micelles (PMs), dendrimers, carbon NPs, nanodiamond (ND), fullerenes, carbon nanotubes (CNTs), graphene oxide (GO), GO nanocomposites and metallic NPs used for combination therapy with various anticancer agents. Nanotechnology has provided the convenient tools for combination therapy. However, for clinical translation, we need continued improvements in the field of nanotechnology.

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Crossref · 10.3390/ijms19103264

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219 of 219 references verified0 citation errors · 0 not checkable

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Figures

Figure 1 The worldwide percentage distribution of cancer types (https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2018.html, Accessed on 11 July 2018).
Figure 1 The worldwide percentage distribution of cancer types (https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2018.html, Accessed on 11 July 2018).CC BY · PubMed Central
Figure 2 The angiogenesis process and treatment of tumors via nanoparticle delivery. (a) Angiogenesis; (b) Drug delivery through NPs; (c) Tumor reduction.
Figure 2 The angiogenesis process and treatment of tumors via nanoparticle delivery. (a) Angiogenesis; (b) Drug delivery through NPs; (c) Tumor reduction.CC BY · PubMed Central
Figure 3 Central dogma of nanoparticles targeting in cancer cells.
Figure 3 Central dogma of nanoparticles targeting in cancer cells.CC BY · PubMed Central
Figure 4 Classification of liposomes based on the lamellarity: (a) Multilamellar vesicles (MLV) are composed of many lipid bilayers and range from 1–5 µm in size; (b) Large unilamellar vesicles (LUV) are in the size range of 100–250 nm with a single lipid bilayer; (c) Small unilamellar vesicles (SUV) consist of a single phospholipid bilayer surrounding an aqueous phase with a size range of 20–100 nm.
Figure 4 Classification of liposomes based on the lamellarity: (a) Multilamellar vesicles (MLV) are composed of many lipid bilayers and range from 1–5 µm in size; (b) Large unilamellar vesicles (LUV) are in the size range of 100–250 nm with a single lipid bilayer; (c) Small unilamellar vesicles (SUV) consist of a single phospholipid bilayer surrounding an aqueous phase with a size range of 20–100 nm.CC BY · PubMed Central
Figure 5 Drug delivery with and without Nanoparticles. Nanoparticle based targeted drug delivery enhanced the antitumor activity due to enhanced and sustained release of drug.
Figure 5 Drug delivery with and without Nanoparticles. Nanoparticle based targeted drug delivery enhanced the antitumor activity due to enhanced and sustained release of drug.CC BY · PubMed Central
Figure 6 Encapsulation mechanism models: drug entrapped in, dissolved in, or dispersed within and adsorbed on: (a) nanocapsules and (b) nanospheres [67].
Figure 6 Encapsulation mechanism models: drug entrapped in, dissolved in, or dispersed within and adsorbed on: (a) nanocapsules and (b) nanospheres [67].CC BY · PubMed Central
Figure 7 Different approaches to modify surfaces of nanoparticles (NPs) to target cancer cells.
Figure 7 Different approaches to modify surfaces of nanoparticles (NPs) to target cancer cells.CC BY · PubMed Central
Figure 8 Combined nano-therapy strategy of CaP nanoparticles containing siRNA and anticancer reagent and their therapeutic effect in cancerous cell. CaP nanoparticles which were assembled with siRNA targeting specific genes is coated with lipids, followed by co-incubation with anticancer drug. The obtained CaNPs/siRNA/DOX are encapsulated by polymers. Internalized CaNPs/siRNA/DOX into cancerous cell are dissolved in endosomal pH through endosomal/lysosomal escape and then released to cytoplasm. Then, siRNA is processed by dicer and RISC system in cytosol and recognize target mRNA to silence the gene expression. Simultaneously, anticancer drug released functions regarding its biological mechanism. Ultimately, both are purposed to induce cell death.
Figure 8 Combined nano-therapy strategy of CaP nanoparticles containing siRNA and anticancer reagent and their therapeutic effect in cancerous cell. CaP nanoparticles which were assembled with siRNA targeting specific genes is coated with lipids, followed by co-incubation with anticancer drug. The obtained CaNPs/siRNA/DOX are encapsulated by polymers. Internalized CaNPs/siRNA/DOX into cancerous cell are dissolved in endosomal pH through endosomal/lysosomal escape and then released to cytoplasm. Then, siRNA is processed by dicer and RISC system in cytosol and recognize target mRNA to silence the gene expression. Simultaneously, anticancer drug released functions regarding its biological mechanism. Ultimately, both are purposed to induce cell death.CC BY · PubMed Central
Figure 9 Combined nano-therapy strategy of MSN containing DOX and AgNPs in cancerous cell. MSNs are loaded with DOX then coated with AgNPs. The obtained DOX/AgNPs/MSN is internalized into cancerous cell via endocytosis and then released to cytosol by endosomal pH through endosomal/lysosomal escape. Released AgNPs resulted in mitochondrial dysfunction by inducing ROS production in mitochondria. DOX released accelerate ROS production, followed by induce oxidative stress in cytosol via DOX semiquinone. DOX also is intercalated into DNA that results in DNA damaging by poisoning of topoisomerase II. Both of AgNPs and DOX finally induce cancer cell death through oxidative stress by increasing ROS and DNA damaging in nucleus. Black colored indicates direction of pathway and red color indicates blocking function.
Figure 9 Combined nano-therapy strategy of MSN containing DOX and AgNPs in cancerous cell. MSNs are loaded with DOX then coated with AgNPs. The obtained DOX/AgNPs/MSN is internalized into cancerous cell via endocytosis and then released to cytosol by endosomal pH through endosomal/lysosomal escape. Released AgNPs resulted in mitochondrial dysfunction by inducing ROS production in mitochondria. DOX released accelerate ROS production, followed by induce oxidative stress in cytosol via DOX semiquinone. DOX also is intercalated into DNA that results in DNA damaging by poisoning of topoisomerase II. Both of AgNPs and DOX finally induce cancer cell death through oxidative stress by increasing ROS and DNA damaging in nucleus. Black colored indicates direction of pathway and red color indicates blocking function.CC BY · PubMed Central

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Citations

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Research works printed but not linked: 1

  1. Mewani, 2004, Analysis of gene expression in breast cancer cells treated with antisense raf oligonucleotide using microarray, Proc. Am. Assoc. Cancer Res., 64, 1209

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Metadata

Authors
Gurunathan, S., Kang, M.-H., Qasim, M., & Kim, J.-H.
Affiliations
Konkuk University (KR)
Corresponding author
  • Gurunathan, Sangiliyandi
  • Kim, Jin-Hoi
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2018-10-20
Volume
19
Issue
10
Pages
3264
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms19103264
PMC
PMC6214025
OpenAlex
W2896053285
Cited by
367
References
220
Citations by year
2026: 26 · 2025: 55 · 2024: 55 · 2023: 51 · 2022: 57 · 2021: 52 · 2020: 47 · 2019: 24
FWCI
2.03
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Keywords
cancer nanomedicine, multidrug resistance, anticancer drug delivery, liposomes, polymeric micelles, dendrimers, carbon nanotubes, graphene oxide, nanodiamonds, C60, metal nanoparticles, angiogenesis, theranostic nanocarriers, drug synergy
MeSH terms
Animals, Antineoplastic Agents, Drug Therapy, Combination, Humans, Nanoparticles

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