Polymers

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16 pages, 3738 KiB

Open AccessArticle

Self-Assembled, Adjuvant/Antigen-Based Nanovaccine Mediates Anti-Tumor Immune Response against Melanoma Tumor

by Santhosh Kalash Rajendrakumar, Adityanarayan Mohapatra, Bijay Singh, Vishnu Revuri, Yong-Kyu Lee, Chang Seong Kim, Chong-Su Cho and In-Kyu Park

Polymers 2018, 10(10), 1063; https://doi.org/10.3390/polym10101063 - 25 Sep 2018

Cited by 16 | Viewed by 5294

Abstract

Malignant melanoma is a highly aggressive type of cancer that requires radical treatment strategies to inhibit the cancer cell progression and metastasis. In recent years, preclinical research and clinical trials on melanoma treatment have been considerably focused on the adjuvant-based immunotherapy for enhancing [...] Read more.

Malignant melanoma is a highly aggressive type of cancer that requires radical treatment strategies to inhibit the cancer cell progression and metastasis. In recent years, preclinical research and clinical trials on melanoma treatment have been considerably focused on the adjuvant-based immunotherapy for enhancing the immune response of innate immune cells against cancer cells. However, the clinical outcome of these adjuvant-based treatments is inadequate due to an improper delivery system for these immune activators to reach the target site. Hence, we developed a vaccine formulation containing tumor lysate protein (TL) and poly I:C (PIC) complexed with positively charged poly (sorbitol-co-polyethylenimine (PEI) (PSPEI). The resulting ionic PSPEI-polyplexed antigen/adjuvant (PAA) (PSPEI-PAA) nanocomplexes were stable at the physiological condition, are non-toxic, and have enhanced intracellular uptake of antigen and adjuvant in immature dendritic cells leading to dendritic cell maturation. In the murine B16F10 tumor xenograft model, PSPEI-PAA nanocomplexes significantly suppressed tumor growth and did not exhibit any noticeable sign of toxicity. The level of matured dendritic cells (CD80+/CD86+ cells) in the tumor draining lymph node of PSPEI-PAA treated tumor mice were enhanced and therefore CD8+ T cells infiltration in the tumor were enriched. Additionally, the cytotoxic T lymphocytes (CTLs) assay involving co-culturing of splenocytes isolated from the PSPEI-PAA-treated mice with that of B16F10 cells significantly revealed enhanced cancer killing by the TL-reactivated CTLs compared to untreated control mice bearing tumor. Therefore, we strongly believe that PSPEI-PAA nanocomplexes could be an efficient antigen/adjuvant delivery system and enhance the antitumor immune response against melanoma tumor in the future clinical trials. Full article

(This article belongs to the Special Issue Polymeric Micro/Nanoparticles for Bio-Medical Applications)

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13 pages, 4413 KiB

Open AccessArticle

Alternating Magnetic Field-Triggered Switchable Nanofiber Mesh for Cancer Thermo-Chemotherapy

by Eri Niiyama, Koichiro Uto, Chun Man Lee, Kazuma Sakura and Mitsuhiro Ebara

Polymers 2018, 10(9), 1018; https://doi.org/10.3390/polym10091018 - 13 Sep 2018

Cited by 40 | Viewed by 5205

Abstract

We have developed a smart anti-cancer fiber mesh that is able to control tumor-killing activity against lung adenocarcinoma precisely. The mesh is capable of carrying large loads of chemotherapeutic drug, paclitaxel (PTX), as well as magnetic nanoparticles (MNPs). The mesh generates heat when [...] Read more.

We have developed a smart anti-cancer fiber mesh that is able to control tumor-killing activity against lung adenocarcinoma precisely. The mesh is capable of carrying large loads of chemotherapeutic drug, paclitaxel (PTX), as well as magnetic nanoparticles (MNPs). The mesh generates heat when the loaded MNPs are activated in an alternating magnetic field (AMF). The mesh is thermo-responsive, so the heat generated can be also used to trigger PTX release from the mesh. An electrospinning method was employed to fabricate the mesh using a copolymer of N-isopropylacrylamide and N-hydroxymethylacrylamide, the phase transition temperature of which was adjusted to the mild-hyperthermia temperature range around 43 °C. In vitro anti-tumor studies demonstrated that both MNP- and PTX-loaded mesh killed about 66% of cells, whereas only PTX-loaded mesh killed about 43% of cells. In a mouse lung cancer model, the thermo-chemotherapy combo displayed enhanced anti-tumor activity and the systemic toxic effects on mice were eliminated due to local release of the chemotherapeutic agents. The proposed fiber system might provide a blueprint to guide the design of the next generation of local drug delivery systems for safe and effective cancer treatment. Full article

(This article belongs to the Special Issue Polymeric Micro/Nanoparticles for Bio-Medical Applications)

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16 pages, 3299 KiB

Open AccessArticle

Inhibition of Tumor Growth via Systemic siRNA Delivery Using Reducible Bile Acid-Conjugated Polyethylenimine

by Yue Yin, Jung Eun Lee, Nak Won Kim, Jong Han Lee, Su Yeon Lim, E Seul Kim, Ji Won Park, Min Sang Lee and Ji Hoon Jeong

Polymers 2018, 10(9), 953; https://doi.org/10.3390/polym10090953 - 27 Aug 2018

Cited by 7 | Viewed by 5802

Abstract

RNA interference (RNAi), mediated by small interfering RNA (siRNA), has been considered as a potential therapeutic agent for cancer owing to its ability to suppress target genes in a sequence-specific manner. In this study, a conjugate of the low molecular weight (M_W [...] Read more.

RNA interference (RNAi), mediated by small interfering RNA (siRNA), has been considered as a potential therapeutic agent for cancer owing to its ability to suppress target genes in a sequence-specific manner. In this study, a conjugate of the low molecular weight (M_W) polyethylenimine (PEI) (M_W 1800) and deoxycholic acid (DA) was further modified with 4-fluorothiophenol (FTP) (TP-DA-PEI) to achieve systemic siRNA delivery. The thiophenol group would be involved with disulfide bonds between the polymer chains and siRNA modified with free thiols (thiol-siRNA) to form and π–π interactions between the pendent aromatic groups and coprostane ring of the bile acid. The TP-DA-PEI conjugates could generate stable nanoparticles with thiol-siRNA. The TP-DA-PEI conjugate not only achieved enhanced intracellular uptake, serum stability, and transfection efficiency, but also showed high accumulation of TP-DA-PEI/thiol-siRNA polyplexes and significant tumor growth inhibition effect in tumor-bearing mice after systemic administration. Full article

(This article belongs to the Special Issue Polymeric Micro/Nanoparticles for Bio-Medical Applications)

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17 pages, 2785 KiB

Open AccessArticle

Bioglass-Incorporated Methacrylated Gelatin Cryogel for Regeneration of Bone Defects

by Song Kwon, Seunghun S. Lee, A. Sivashanmugam, Janet Kwon, Seung Hyun L. Kim, Mi Yeon Noh, Seong Keun Kwon, R. Jayakumar and Nathaniel S. Hwang

Polymers 2018, 10(8), 914; https://doi.org/10.3390/polym10080914 - 14 Aug 2018

Cited by 53 | Viewed by 8985

Abstract

Cryogels have recently gained interest in the field of tissue engineering as they inherently possess an interconnected macroporous structure. Considered to be suitable for scaffold cryogel fabrication, methacrylated gelatin (GelMA) is a modified form of gelatin valued for its ability to retain cell [...] Read more.

Cryogels have recently gained interest in the field of tissue engineering as they inherently possess an interconnected macroporous structure. Considered to be suitable for scaffold cryogel fabrication, methacrylated gelatin (GelMA) is a modified form of gelatin valued for its ability to retain cell adhesion site. Bioglass nanoparticles have also attracted attention in the field due to their osteoinductive and osteoconductive behavior. Here, we prepare methacrylated gelatin cryogel with varying concentration of bioglass nanoparticles to study its potential for bone regeneration. We demonstrate that an increase in bioglass concentration in cryogel leads to improved mechanical property and augmented osteogenic differentiation of mesenchymal cells during in vitro testing. Furthermore, in vivo testing in mice cranial defect model shows that highest concentration of bioglass nanoparticles (2.5 w/w %) incorporated in GelMA cryogel induces the most bone formation compared to the other tested groups, as studied by micro-CT and histology. The in vitro and in vivo results highlight the potential of bioglass nanoparticles incorporated in GelMA cryogel for bone regeneration. Full article

(This article belongs to the Special Issue Polymeric Micro/Nanoparticles for Bio-Medical Applications)

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11 pages, 12618 KiB

Open AccessArticle

Hypoxia-Responsive Mesoporous Nanoparticles for Doxorubicin Delivery

by Shakera Khatoon, Hwa Seung Han, Jueun Jeon, N. Vijayakameswara Rao, Dae-Woong Jeong, M. Ikram, T. Yasin, Gi-Ra Yi and Jae Hyung Park

Polymers 2018, 10(4), 390; https://doi.org/10.3390/polym10040390 - 1 Apr 2018

Cited by 25 | Viewed by 6481

Abstract

Hypoxia, or low oxygen tension, is a common feature of solid tumors. Here, we report hypoxia-responsive mesoporous silica nanoparticles (HR-MSNs) with a 4-nitroimidazole-β-cyclodextrin (NI-CD) complex that is acting as the hypoxia-responsive gatekeeper. When these CD-HR-MSNs encountered a hypoxic environment, the nitroimidazole (NI) gatekeeper [...] Read more.

Hypoxia, or low oxygen tension, is a common feature of solid tumors. Here, we report hypoxia-responsive mesoporous silica nanoparticles (HR-MSNs) with a 4-nitroimidazole-β-cyclodextrin (NI-CD) complex that is acting as the hypoxia-responsive gatekeeper. When these CD-HR-MSNs encountered a hypoxic environment, the nitroimidazole (NI) gatekeeper portion of CD-HR-MSNs disintegrated through bioreduction of the hydrophobic NI state to the hydrophilic NI state. Under hypoxic conditions, the release rate of doxorubicin (DOX) from DOX-loaded CD-HR-MSNs (DOX-CD-HR-MSNs) increased along with the disintegration of the gatekeeper. Conversely, DOX release was retarded under normoxic conditions. In vitro experiments confirmed that DOX-CD-HR-MSNs exhibit higher toxicity to hypoxic cells when compared to normoxic cells. Confocal microscopy images indicated that DOX-CD-HR-MSNs effectively release DOX into SCC-7 cells under hypoxic conditions. These results demonstrate that CD-HR-MSNs can release drugs in a hypoxia-responsive manner, and thus are promising drug carriers for hypoxia-targeted cancer therapy. Full article

(This article belongs to the Special Issue Polymeric Micro/Nanoparticles for Bio-Medical Applications)

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Review

Jump to: Research

16 pages, 2980 KiB

Open AccessReview

Contemporary Polymer-Based Nanoparticle Systems for Photothermal Therapy

by Jeremy B. Vines, Dong-Jin Lim and Hansoo Park

Polymers 2018, 10(12), 1357; https://doi.org/10.3390/polym10121357 - 7 Dec 2018

Cited by 46 | Viewed by 5735

Abstract

Current approaches for the treatment of cancer, such as chemotherapy, radiotherapy, immunotherapy, and surgery, are limited by various factors, such as inadvertent necrosis of healthy cells, immunological destruction, or secondary cancer development. Hyperthermic therapy is a promising strategy intended to mitigate many of [...] Read more.

Current approaches for the treatment of cancer, such as chemotherapy, radiotherapy, immunotherapy, and surgery, are limited by various factors, such as inadvertent necrosis of healthy cells, immunological destruction, or secondary cancer development. Hyperthermic therapy is a promising strategy intended to mitigate many of the shortcomings associated with traditional therapeutic approaches. However, to utilize this approach effectively, it must be targeted to specific tumor sites to prevent adverse side effects. In this regard, photothermal therapy, using intravenously-administered nanoparticle materials capable of eliciting hyperthermic effects in combination with the precise application of light in the near-infrared spectrum, has shown promise. Many different materials have been proposed, including various inorganic materials such as Au, Ag, and Germanium, and C-based materials. Unfortunately, these materials are limited by concerns about accumulation and potential cytotoxicity. Polymer-based nanoparticle systems have been investigated to overcome limitations associated with traditional inorganic nanoparticle systems. Some of the materials that have been investigated for this purpose include polypyrrole, poly-(3,4-ethylenedioxythiophene):poly(4-styrenesulfonate) (PEDOT:PSS), polydopamine, and polyaniline. The purpose of this review is to summarize these contemporary polymer-based nanoparticle technologies to acquire an understanding of their current applications and explore the potential for future improvements. Full article

(This article belongs to the Special Issue Polymeric Micro/Nanoparticles for Bio-Medical Applications)

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15 pages, 1395 KiB

Open AccessReview

Hyaluronic Acid-Based Nanomaterials for Cancer Therapy

by Jin Hong Kim, Myeong Ju Moon, Dong Yi Kim, Suk Hee Heo and Yong Yeon Jeong

Polymers 2018, 10(10), 1133; https://doi.org/10.3390/polym10101133 - 12 Oct 2018

Cited by 130 | Viewed by 11660

Abstract

Hyaluronic acid (HA) is a nonsulfated glycosaminoglycan and a major component of the extracellular matrix. HA is overexpressed by numerous tumor cells, especially tumor-initiating cells. HA-based nanomaterials play in importance role in drug delivery systems. HA is used in various types of nanomaterials [...] Read more.

Hyaluronic acid (HA) is a nonsulfated glycosaminoglycan and a major component of the extracellular matrix. HA is overexpressed by numerous tumor cells, especially tumor-initiating cells. HA-based nanomaterials play in importance role in drug delivery systems. HA is used in various types of nanomaterials including micelle, polymersome, hydrogel, and inorganic nanoparticle formulations. Many experiments show that HA-based nanomaterials can serve as a platform for targeted chemotherapy, gene therapy, immunotherapy, and combination therapy with good potential for future biomedical applications in cancer treatment. Full article

(This article belongs to the Special Issue Polymeric Micro/Nanoparticles for Bio-Medical Applications)

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36 pages, 12675 KiB

Open AccessReview

Incorporation of Conductive Materials into Hydrogels for Tissue Engineering Applications

by Ji Hong Min, Madhumita Patel and Won-Gun Koh

Polymers 2018, 10(10), 1078; https://doi.org/10.3390/polym10101078 - 28 Sep 2018

Cited by 151 | Viewed by 15603

Abstract

In the field of tissue engineering, conductive hydrogels have been the most effective biomaterials to mimic the biological and electrical properties of tissues in the human body. The main advantages of conductive hydrogels include not only their physical properties but also their adequate [...] Read more.

In the field of tissue engineering, conductive hydrogels have been the most effective biomaterials to mimic the biological and electrical properties of tissues in the human body. The main advantages of conductive hydrogels include not only their physical properties but also their adequate electrical properties, which provide electrical signals to cells efficiently. However, when introducing a conductive material into a non-conductive hydrogel, a conflicting relationship between the electrical and mechanical properties may develop. This review examines the strengths and weaknesses of the generation of conductive hydrogels using various conductive materials such as metal nanoparticles, carbons, and conductive polymers. The fabrication method of blending, coating, and in situ polymerization is also added. Furthermore, the applications of conductive hydrogel in cardiac tissue engineering, nerve tissue engineering, and bone tissue engineering and skin regeneration are discussed in detail. Full article

(This article belongs to the Special Issue Polymeric Micro/Nanoparticles for Bio-Medical Applications)

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17 pages, 1598 KiB

Open AccessReview

Hydrogel Biomaterials for Stem Cell Microencapsulation

by Goeun Choe, Junha Park, Hansoo Park and Jae Young Lee

Polymers 2018, 10(9), 997; https://doi.org/10.3390/polym10090997 - 6 Sep 2018

Cited by 100 | Viewed by 11599

Abstract

Stem cell transplantation has been recognized as a promising strategy to induce the regeneration of injured and diseased tissues and sustain therapeutic molecules for prolonged periods in vivo. However, stem cell-based therapy is often ineffective due to low survival, poor engraftment, and a [...] Read more.

Stem cell transplantation has been recognized as a promising strategy to induce the regeneration of injured and diseased tissues and sustain therapeutic molecules for prolonged periods in vivo. However, stem cell-based therapy is often ineffective due to low survival, poor engraftment, and a lack of site-specificity. Hydrogels can offer several advantages as cell delivery vehicles, including cell stabilization and the provision of tissue-like environments with specific cellular signals; however, the administration of bulk hydrogels is still not appropriate to obtain safe and effective outcomes. Hence, stem cell encapsulation in uniform micro-sized hydrogels and their transplantation in vivo have recently garnered great attention for minimally invasive administration and the enhancement of therapeutic activities of the transplanted stem cells. Several important methods for stem cell microencapsulation are described in this review. In addition, various natural and synthetic polymers, which have been employed for the microencapsulation of stem cells, are reviewed in this article. Full article

(This article belongs to the Special Issue Polymeric Micro/Nanoparticles for Bio-Medical Applications)

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25 pages, 2705 KiB

Open AccessReview

Cell Membrane-Camouflaged Nanoparticles: A Promising Biomimetic Strategy for Cancer Theragnostics

by Veena Vijayan, Saji Uthaman and In-Kyu Park

Polymers 2018, 10(9), 983; https://doi.org/10.3390/polym10090983 - 3 Sep 2018

Cited by 135 | Viewed by 12091

Abstract

Biomimetic functionalization of nanoparticles through camouflaging with cellular membranes has emerged as a promising strategy for cancer theragnostics. Cellular membranes used for camouflaging nanoparticles are generally isolated from blood cells, immune cells, cancer cells, and stem cells. The camouflaging strategy of wrapping nanoparticles [...] Read more.

Biomimetic functionalization of nanoparticles through camouflaging with cellular membranes has emerged as a promising strategy for cancer theragnostics. Cellular membranes used for camouflaging nanoparticles are generally isolated from blood cells, immune cells, cancer cells, and stem cells. The camouflaging strategy of wrapping nanoparticles with cellular membranes allows for superior tumor targeting through self-recognition, homotypic targeting and prolonged systematic circulation, thereby aiding in effective tumor therapy. In this review, we emphasized the various types of cellular membrane-camouflaged nanoparticles, their mechanisms in targeted therapy and various biomimetic strategies for anti-cancer therapy. Full article

(This article belongs to the Special Issue Polymeric Micro/Nanoparticles for Bio-Medical Applications)

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14 pages, 1734 KiB

Open AccessReview

Near-Infrared-Responsive Cancer Photothermal and Photodynamic Therapy Using Gold Nanoparticles

by Hyung Shik Kim and Dong Yun Lee

Polymers 2018, 10(9), 961; https://doi.org/10.3390/polym10090961 - 30 Aug 2018

Cited by 186 | Viewed by 21587

Abstract

Rapid growth of nanotechnology is one of the most quickly emerging tendencies in cancer therapy. Gold nanoparticles roused a distinctive interest in the field, due to their incomparable light-to-thermal energy conversion efficiency, and their ability to load and deliver a variety of anticancer [...] Read more.

Rapid growth of nanotechnology is one of the most quickly emerging tendencies in cancer therapy. Gold nanoparticles roused a distinctive interest in the field, due to their incomparable light-to-thermal energy conversion efficiency, and their ability to load and deliver a variety of anticancer drugs. Therefore, simultaneous photothermal (PTT) and photodynamic (PDT) cancer therapy is available by the role of the thermal agent of the gold nanoparticle itself and the drug delivery carrier for photosensitizer (PS) transport. In this review, the physical, chemical, and biological properties of gold nanoparticle, which can promote PTT and PDT efficiency, are briefly demonstrated, and we highlight recent progression in the development of PS-containing gold nanocomposites for effective cancer therapy. Full article

(This article belongs to the Special Issue Polymeric Micro/Nanoparticles for Bio-Medical Applications)

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18 pages, 1376 KiB

Open AccessReview

Oral Vaccine Delivery for Intestinal Immunity—Biological Basis, Barriers, Delivery System, and M Cell Targeting

by Sung Hun Kang, Seok Jin Hong, Yong-Kyu Lee and Sungpil Cho

Polymers 2018, 10(9), 948; https://doi.org/10.3390/polym10090948 - 27 Aug 2018

Cited by 58 | Viewed by 10225

Abstract

Most currently available commercial vaccines are delivered by systemic injection. However, needle-free oral vaccine delivery is currently of great interest for several reasons, including the ability to elicit mucosal immune responses, ease of administration, and the relatively improved safety. This review summarizes the [...] Read more.

Most currently available commercial vaccines are delivered by systemic injection. However, needle-free oral vaccine delivery is currently of great interest for several reasons, including the ability to elicit mucosal immune responses, ease of administration, and the relatively improved safety. This review summarizes the biological basis, various physiological and immunological barriers, current delivery systems with delivery criteria, and suggestions for strategies to enhance the delivery of oral vaccines. In oral vaccine delivery, basic requirements are the protection of antigens from the GI environment, targeting of M cells and activation of the innate immune response. Approaches to address these requirements aim to provide new vaccines and delivery systems that mimic the pathogen’s properties, which are capable of eliciting a protective mucosal immune response and a systemic immune response and that make an impact on current oral vaccine development. Full article

(This article belongs to the Special Issue Polymeric Micro/Nanoparticles for Bio-Medical Applications)

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20 pages, 6787 KiB

Open AccessReview

Stimuli-Responsive Polypeptides for Biomedical Applications

by DaeYong Lee, N. Sanoj Rejinold, Seong Dong Jeong and Yeu-Chun Kim

Polymers 2018, 10(8), 830; https://doi.org/10.3390/polym10080830 - 27 Jul 2018

Cited by 19 | Viewed by 5482

Abstract

Stimuli-responsive polypeptides have gained attention because desirable bioactive properties can be easily imparted to them while keeping their biocompatibility and biodegradability intact. In this review, we summarize the most recent advances in various stimuli-responsive polypeptides (pH, reduction, oxidation, glucose, adenosine triphosphate (ATP), and [...] Read more.

Stimuli-responsive polypeptides have gained attention because desirable bioactive properties can be easily imparted to them while keeping their biocompatibility and biodegradability intact. In this review, we summarize the most recent advances in various stimuli-responsive polypeptides (pH, reduction, oxidation, glucose, adenosine triphosphate (ATP), and enzyme) over the past five years. Various synthetic strategies exploited for advanced polypeptide-based materials are introduced, and their applicability in biomedical fields is discussed. The recent polypeptides imparted with new stimuli-responsiveness and their novel chemical and physical properties are explained in this review. Full article

(This article belongs to the Special Issue Polymeric Micro/Nanoparticles for Bio-Medical Applications)

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