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Carbohydrate-Based Nanogels as Drug and Gene Delivery Systems
Uthaman, S.,Maya, S.,Jayakumar, R.,Cho, C.-S.,Park, I.-K. American Scientific Publishers 2014 Journal of Nanoscience and Nanotechnology Vol.14 No.1
Nanogels are hydrogels with nanometer-scale three-dimensional networks of physically or chemically cross-linked chains. Nanogels have attracted much interest in recent years for various biomedical applications such as drug delivery systems and bioimaging owing to their specific properties of size tunability and intrinsic hydrophilic surfaces. Nanogels are generally classified either as natural polymer-based or synthetic polymer-based nanogels. Natural polymer-based nanogels are considered better candidates for drug delivery than synthetic polymer-based nanogels. This review summarizes the role of natural polymer-based nanogels, especially carbohydrate-based nanogels as drug and gene delivery systems.
Green synthesis of bioactive polysaccharide-capped gold nanoparticles for lymph node CT imaging
Uthaman, Saji,Kim, Hyeon Sik,Revuri, Vishnu,Min, Jung-Joon,Lee, Yong-kyu,Huh, Kang Moo,Park, In-Kyu Elsevier 2018 Carbohydrate polymers Vol.181 No.-
<P><B>Abstract</B></P> <P>The development of biologically targeted contrast agents for X-ray computed tomography (CT) imaging remains a major challenge. Here, we investigated a green chemistry-based synthesis of lymph node-targeted mannan-capped gold nanoparticles (M-GNPs) as a CT contrast agent. In this study, mannan was used as a reducing and stabilizing agent for gold nanoparticles (AuNPs). M-GNPs were readily internalized by antigen-presenting cells (APCs) through mannose receptors-mediated endocytosis. The M-GNPs, which had a spherical morphology, had an average diameter of 9.18±0.71nm and surface plasmon resonance (SPR) absorption spectra with maximal absorption at 522nm. The M-GNPs displayed a concentration-based X-ray attenuation property with a maximum Hounsfield unit (HU) value of 303.2±10.83. The local administration of M-GNPs led to significantly enhanced X-ray contrast for the imaging of popliteal lymph nodes. These findings demonstrated that M-GNPs can be used as biologically targeted contrast agents for CT imaging.</P> <P><B>Highlights</B></P> <P> <UL> <LI> M-GNPs as CT contrast agent for lymph node imaging. </LI> <LI> M-GNPs were spherical nanoparticles with an average diameter of 9.18±0.71nm. </LI> <LI> M-GNPs exhibited mannose receptor mediated endocytosis in antigen presenting cells. </LI> <LI> Local administration of M-GNPs led to significantly enhanced X-ray imaging of popliteal lymph nodes. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
IR 780-loaded hyaluronic acid micelles for enhanced tumor-targeted photothermal therapy
Uthaman, Saji,Mathew, Ansuja Pulickal,Park, Hyeong Ju,Lee, Byeong-Il,Kim, Hyung-Seok,Huh, Kang Moo,Park, In-Kyu Elsevier 2018 Carbohydrate polymers Vol.181 No.-
<P><B>Abstract</B></P> <P>In this study, we propose using IR 780-loaded, CD44-targeted hyaluronic acid-based micelles (HA-IR 780) for enhanced photothermal therapy (PTT) effects in tumors. Two kinds of HA-C18 micelles were synthesized from different C18 feed ratios with degree of substitution of 3% and 13% respectively. Three different IR 780 weight percentages were used for micelle formation with loading content of 4.6%, 7.9%, and 10.3% respectively. The IC<SUB>50</SUB> value of HA-IR 780 in TC1 cells was 21.89μgmL<SUP>−1</SUP> (32.81μM). Upon irradiation of the tumor site with an 808-nm laser (2Wcm<SUP>−2</SUP>) for 2min, the temperature in the tumor in the HA-IR 780-treated groups reached 49.9°C which exceeds the temperature threshold to induce irreversible tissue damage. Toxicity studies showed that HA-IR 780 does not cause any adverse effects in organs, including heart, liver, lungs, kidney and spleen, although it selectively caused cell damage in the tumor region upon laser irradiation. Therefore, the present study suggests that HA-IR 780 can cause selective cell death in tumor regions due to its enhanced tumor-targeting and photothermal capabilities.</P> <P><B>Highlights</B></P> <P> <UL> <LI> IR 780-loaded hyaluronic acid-based micelles (HA-IR 780) for photothermal therapy. </LI> <LI> Intravenously administered HA-IR 780 selectively accumulated in tumors by 24h. </LI> <LI> HA-IR 780 exhibited CD44- and EPR-based tumor accumulation. </LI> <LI> Upon irradiation HA-IR 780 causes photothermic ablation in tumor region. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
Tumor microenvironment-responsive nanoparticles for cancer theragnostic applications
Saji Uthaman,허강무,박인규 한국생체재료학회 2018 생체재료학회지 Vol.22 No.3
Background: Cancer is one of the deadliest threats to human health. Abnormal physiochemical conditions and dysregulated biosynthetic intermediates in the tumor microenvironment (TME) play a significant role in modulating cancer cells to evade or defend conventional anti-cancer therapy such as surgery, chemotherapy and radiotherapy. One of the most important challenges in the development of anti-tumor therapy is the successful delivery of therapeutic and imaging agents specifically to solid tumors. Main body: The recent progresses in development of TME responsive nanoparticles offers promising strategies for combating cancer by making use of the common attributes of tumor such as acidic and hypoxic microenvironments. In this review, we discussed the prominent strategies utilized in the development of tumor microenvironment-responsive nanoparticles and mode of release of therapeutic cargo. Conclusion: Tumor microenvironment-responsive nanoparticles offers a universal approach for anti-cancer therapy.
Saji Uthaman,Shameer Pillarisetti,허강무,Chong-SuCho,박인규 한국공업화학회 2021 Journal of Industrial and Engineering Chemistry Vol.97 No.-
Tumor metastasis is associated with high mortality in breast cancer patients. Although photothermaltherapy (PTT) has arisen as a promising anticancer treatment approach, PTT-based monotherapies stillfail to eradicate advanced cancers due to the immunosuppressive microenvironment. Herein, wesynthesized drug-dye-lipid-like micelles composed of thermoresponsive poloxamer conjugated withlinoleic acid (PCLA) loaded with a chemotherapeutic drug doxorubicin (DOX) and a near-infrared dye IR-780 (PCLA-ID) to enhance antitumor immunity against progressive metastatic breast cancers. Intravenous administration of sub-100 nm sized PCLA-ID in breast tumor-bearing mice followed bylocal laser irradiation eliminated not only primary tumors, but also untreated distant tumors (abscopaleffect). The combinatorial treatment of apoptosis-inducing PCLA-ID, which contained DOX at asubtherapeutic dose, and PTT augmented the maturation of tumor-draining lymph nodes, theupregulation of cytotoxic T lymphocytes, and the suppression of regulatory T cells in untreatedsecondary tumors. These events prevented lung metastasis in tumor-bearing mice after re-challengingwith a second injection of breast cancer cells. We conclude that PCLA-ID nanoparticles can enhanceimmunogenic cell death, representing a promising strategy for triggering immune responses againstadvanced metastatic breast cancers.