Emerging 2D material-based nanocarrier for cancer therapy beyond graphene

Wang, Yingwei,Qiu, Meng,Won, Miae,Jung, Eugeine,Fan, Taojian,Xie, Ni,Chi, Sung-Gil,Zhang, Han,Kim, Jong Seung Elsevier 2019 Coordination Chemistry Reviews Vol.400 No.-

<P><B>Abstract</B></P> <P>2D materials (e.g., graphene, graphene analogues), with unique physical and chemical properties, shows intriguing potential for the realization of versatile biomedical applications. Tremendous attention has been attracted on 2D material based nanocarriers, which play a crucial role in therapeutic drug, gene, and biomedical agent delivery for cancer theranostics. This review provides an up-to-date review on the development of nanocarriers based on 2D materials beyond graphene, including basic and emerging synthesis methods, the catalog of 2D material-based nanocarriers, biosafety, surface functional engineering, the realization of stimuli-responsive controllable release and biomedical applications. Among the properties and performance to be summarized, there is particular focus on nanocarriers loading capability, biosafety, and therapy efficiency and so on. Finally, by addressing major issues and challenges, some prospects for future directions in this area are provided.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Highlight the emerging 2D material based nanocarriers for biomedical applications. </LI> <LI> Summarized surface engineering strategy used in nanocarriers. </LI> <LI> Overview the biomedical application of 2D material nanocarriers. </LI> <LI> Give a guide to design stimuli-responsive controllable drug release strategy. </LI> <LI> Proposed insightful prospects for the future development of 2D material based nanocarriers application. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Multifunctional Hybrid Nanocarrier: Magnetic CNTs Ensheathed with Mesoporous Silica for Drug Delivery and Imaging System

Singh, Rajendra K.,Patel, Kapil D.,Kim, Jung-Ju,Kim, Tae-Hyun,Kim, Joong-Hyun,Shin, Ueon Sang,Lee, Eun-Jung,Knowles, Jonathan C.,Kim, Hae-Won American Chemical Society 2014 ACS APPLIED MATERIALS & INTERFACES Vol.6 No.4

<P>Here we communicate the development of a novel multifunctional hybrid nanomaterial, magnetic carbon nanotubes (CNTs) ensheathed with mesoporous silica, for the simultaneous applications of drug delivery and imaging. Magnetic nanoparticles (MNPs) were first decorated onto the multiwalled CNTs, which was then layered with mesoporous silica (<I>m</I>SiO<SUB>2</SUB>) to facilitate the loading of bioactive molecules to a large quantity while exerting magnetic properties. The hybrid nanomaterial showed a high mesoporosity due to the surface-layered <I>m</I>SiO<SUB>2</SUB>, and excellent magnetic properties, including magnetic resonance imaging in vitro and in vivo. The mesoporous and magnetic hybrid nanocarriers showed high loading capacity for therapeutic molecules including drug gentamicin and protein cytochrome C. In particular, genetic molecule siRNA was effectively loaded and then released over a period of days to a week. Furthermore, the hybrid nanocarriers exhibited a high cell uptake rate through magnetism, while eliciting favorable biological efficacy within the cells. This novel hybrid multifunctional nanocarrier may be potentially applicable as drug delivery and imaging systems.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/aamick/2014/aamick.2014.6.issue-4/am4056936/production/images/medium/am-2013-056936_0006.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/am4056936'>ACS Electronic Supporting Info</A></P>

Synthesis of a new polymer from arginine for the preparation of antioxidant, pH-sensitive, and photoluminescence nanocomposite as a cancer drugs carrier

Robab Aslani,Hassan Namazi 한국공업화학회 2022 Journal of Industrial and Engineering Chemistry Vol.112 No.-

In this study, we aimed to synthesize a new photoluminescent nanocomposite based on hyperbranchedpolymers derived from arginine through an easy method for drug delivery application. Hence, a newhyperbranched polymer (HBPAC) via co-polymerization of citric acid (as A3 type monomer) and Larginine(as AB2 type monomer) was synthesized and composited with glucose-derived quantum dot(GluQD) to obtain the HBPAC-GluQD nanocarrier. The HBPAC-GluQD was characterized, and its potentialwas studied as a nanocarrier. The particles size of the nanocomposite was about 90–200 nm. The antioxidantstudy of the HBPAC-GluQD revealed its excellent antioxidant properties. Also, the prepared HBPACGluQDshowed photoluminescence (PL) in the blue range under 322 nm excitation with a QY of 72.8%. Invitro bioimaging investigations determined that HBPAC-GluQD has a potential for bioimaging applications. In-vitro release investigation of the HBPAC-GluQD nanocarrier exhibited that the composite haspH-responsive behavior and showed that the highest release happens at pH 5. Also, the stability, redblood cells compatibility, and MTT assay were evaluated. The obtained results showed that theHBPAC-GluQD as a nanocarrier is stable enough, biodegradable, and hemocompatible in physiologicalcondition. Also, apoptosis, cellular uptake, and MTT analysis showed that the HBPAC-GluQD-DOX/MTXcould efficiently induce cellular apoptosis.

A pH-Sensitive Polymer for Cancer Targeting Prepared by One-Step Modulation of Functional Side Groups

심태훈,한상명,임채민,원웅록,이은성,윤유석,오경택 한국고분자학회 2019 Macromolecular Research Vol.27 No.8

Nanocarriers with pH-sensitive functionality are of great interest in the development of pH-dependent drug release compounds in acidic tumor microenvironments. A new polyelectrolyte block copolymer, poly[(benzyl-L-aspartate)-co-(N- (3-aminopropyl) imidazole-L-aspartamide)]-poly(ethylene glycol) (PABI-PEG), was prepared by one-step modulation to produce pH-sensitive nanocarriers. PABI-PEG formed a stable nanocarrier at pH values above 7.4 and was destabilized in acidic conditions (pH 6.5) through the protonation of the imidazole groups. Docetaxel loaded micelle (DLM) exhibited pH-dependent drug release through structural conversion due to the protonation of the imidazole groups on the PABI block. The critically low micelle concentration of PABI-PEG at physiological pH and the pH-dependent drug release would result to high stability and restrict drug loss during systemic circulation which may lower the toxicity of normal tissue to physiological pH. Additionally, the extracellular tumor pH (<7.0) and early endosomal pH (<6.5) environments triggered the disintegration of micelles, producing higher drug release compared to other normal tissues and blood (pH 7.4). Therefore, PABI-PEG may be a pHsensitive drug delivery method for cancer chemotherapy.

Polymeric nanocarrier systems for photodynamic therapy

Li Li,허강무 한국생체재료학회 2015 생체재료학회지 Vol.19 No.1

Photodynamic therapy (PDT) is an emerging treatment modality that involves the combined action of photosensitizers (PSs) and light for treatment of solid tumor and other diseases. Although this therapeutic method has been considered as an alternative to classical cancer treatments, clinical PDT requires further advances in selectivity and therapeutic efficacy to overcome numerous shortages related to conventional PDT. In this regard, great efforts have been devoted to the development of polymeric nanocarrier-encapsulated PSs for targeted PDT, aiming at improvement of water solubility and tumor-specificity of hydrophobic PSs. Here, we discuss the general concepts and considerations of polymeric nanocarriers for efficient delivery of PSs. In recent, the amphiphilic PS-polymer conjugate-based self-quenchable nanoparticles and PS-polymer-conjugate/quencher nanocomplexes have emerged as an attractive delivery platform for efficient and reliable PDT. They can incorporate and deliver the PS in a photodynamically inactive state but demonstrate cytotoxic effects by tumor environment-sensitive activation mechanisms, so that the photodynamic cancer treatment can achieve maximum target specificity. Here, we report the recent achievements on the development of activatable PS formulations based on PS-polymer conjugates.

Development and Characterization of Polyethylenimine Nanocarriers Processed by an Inductive Thermospraying Technique

Poh Yit Foo,Hui Shan Cheok,Thiago Coutinho Cavalcanti,Grace Lim Yik Shi,곽은아,Justyn Jaworski 한국고분자학회 2016 Macromolecular Research Vol.24 No.6

Using a high temperature vaporizing spray approach to nanoparticle fabrication, we reveal a straightforward process for the formation of polyethyleneimine (PEI) scaffold based hydrogel nanoparticles. With PEI as the polymeric skeleton, we demonstrate the possibility for capture and release of small molecule, protein, nucleic acid, or colloidal cargo. Here, we provide evidence for use of the PEI nanoparticles as versatile nanocarriers. Moreover, we provide characterization of the nanoparticles produced by our inductive heat spraying approach along with determination of the loading capacity for the various cargos. We also observed the release profiles for a traceable small molecule in our proof of concept work. While linear chains or dendrimers of PEI are well-known to be cytotoxic, we revealed that our larger scale nanoparticles (which are in the range of 400-500 nm) have no noticeable cytotoxicity in vitro. With this initial work, we expect the intrinsic capabilities of the PEI nanoparticle scaffold demonstrated here in terms of molecular capture may possibly be utilized for effective nanocarriers upon future tuning of the nanoparticle size as to avoid any rapid clearance.

Osteopromoting Reservoir of Stem Cells: Bioactive Mesoporous Nanocarrier/Collagen Gel through Slow-Releasing FGF18 and the Activated BMP Signaling

Mahapatra, Chinmaya,Singh, Rajendra K.,Kim, Jung-Ju,Patel, Kapil D.,Perez, Roman A.,Jang, Jun-Hyeog,Kim, Hae-Won American Chemical Society 2016 ACS APPLIED MATERIALS & INTERFACES Vol.8 No.41

<P>Providing an osteogenic stimulatory environment is a key strategy to construct stem cell-based bone-equivalent tissues. Here we design a stem cell delivering gel matrix made of collagen (Col) with bioactive glass nanocarriers (BGn) that incorporate osteogenic signaling molecule, fibroblast growth factor 18 (FGF18), a reservoir considered to cultivate and promote osteogenesis of mesenchymal stem cells (MSCs). The presence of BGn in the gel was shown to enhance the osteogenic differentiation of MSCs, possibly due to the therapeutic role of ions released. The mesoporous nature of BGn was effective in loading FGF18 at large quantity, and the FGF18 release from the BGn-Col gel matrix was highly sustainable with almost a zero-order kinetics, over 4 weeks as confirmed by the green fluorescence protein signal change. The released FGF18 was effective in accelerating osteogenesis (alkaline phosphatase activity and bone related gene expressions) and bone matrix formation (osteopontin, bone sialoprotein, and osteocalcin production) of MSCs. This was attributed to the bone morphogenetic protein (BMP) signaling pathway, where the FGF18 release stimulated the endogenous secretion of BMP2 and the downstream signal Smad1/5/8. Taken together, the FGF18-BGn/Col gel is considered an excellent osteopromoting depot to support and signal MSCs for bone tissue engineering.</P>

Heparin-Conjugated Pluronic Nanogels as Multi-Drug Nanocarriers for Combination Chemotherapy

Joung, Yoon Ki,Jang, Ji Young,Choi, Jong Hoon,Han, Dong Keun,Park, Ki Dong American Chemical Society 2013 Molecular pharmaceutics Vol.10 No.2

<P>Combination chemotherapy using more than two therapeutic agents with different modes of action is a promising strategy that can be used to enhance the therapeutic efficacy of cancer treatment, even though it is a complicated treatment modality. The aim of this study was to investigate how a novel multidrug nanocarrier is effective for combination chemotherapy <I>in vitro</I> and, more specifically, whether combined agents with different modes of action and physicochemical properties show synergistic cytotoxicity with the use of this nanocarrier. A heparin–Pluronic (Hep–Pr) nanogel encapsulating both paclitaxel and DNase was shown to be efficient for intracellular delivery with respect to size, encapsulation efficiency, and intracellular uptake/fates. As a result of these properties, a Hep–Pr nanogel combined with paclitaxel and DNase exhibited a dose-dependent synergistic cytotoxicity compared to single drug and free-drug treatments, whose combination indices were 0.93 and 0.45 at higher concentrations (250 and 500 μg/mL). Therefore, Hep–Pr nanogels have the potential to deliver multitherapeutic agents with different characteristics and thereby enhance the therapeutic efficacy of combination cancer chemotherapy.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/mpohbp/2013/mpohbp.2013.10.issue-2/mp300480v/production/images/medium/mp-2012-00480v_0010.gif'></P>

Nanosized Ultrasound Enhanced-Contrast Agent for in Vivo Tumor Imaging via Intravenous Injection

Kim, Manse,Lee, Jong Hyun,Kim, Se Eun,Kang, Seong Soo,Tae, Giyoong American Chemical Society 2016 ACS APPLIED MATERIALS & INTERFACES Vol.8 No.13

<P>To enhance the detection limit of ultrasound (US) imaging, ultrasound enhanced-contrast agents (UECAs) that can go preferentially to the target tissue such as a tumor and amplify the US signal have been developed. However, nanosized UECAs among various UECAs developed are very limited to clearly demonstrate proper ability for selective tumor detection by US imaging upon their intravenous injection. In this study, we prepared CaCO3 nanoparticles that were formed inside a flexible and biocompatible pluronic-based nanocarrier. This nanosized UECA was stable in serum-containing media and generated CO2, more preferentially at low pH; thus, it could be detected by US imaging. After intravenous injection into tumor-bearing mice, this nanosized UECA showed a significant US contrast enhancement at the tumor site in 1 h, in contrast to no change in the liver, followed by a rapid clearance from the body in 24 h. Therefore, the present nanosized UECA could be applied as an effective diagnostic modality for in vivo tumor imaging by ultrasonography.</P>

1P-519 Artificial Exosomes Fabricated by Tailored Conjugation of Fusogen to Lipid/Polymer Hybrid Vesicles

강정이,김슬기,김진웅 한국공업화학회 2017 한국공업화학회 연구논문 초록집 Vol.2017 No.1

Exosomes are cell-derived vesicles offer active yet specific cellular attraction to drug delivery applications. In this study, we propose a novel active drug delivery system which is established by using lipid/polymer hybrid vesicles with fusogenic peptide conjugates. The lipid/polymer hybrid vesicles are fabricated by co-assembly of phosphatidylcholine and poly(ethylene oxide)-b-poly(dimethyl siloxane)-b-poly(ethylene oxide). Thanks to large size and slow dynamics of amphiphilic triblock copolymers at the bilayer membrane, the hybrid vesicles show long-circulating time and high drug loading efficiency. To evaluate the cell affinity of fusogenic exosomes, the interaction force of the exosomes with cells is characterized via surface force apparatus. Finally, in vitro cell-penetration study demonstrates the practical applicability of our artificial exosome as a remarkable cell delivery nanocarrier.