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1.
Biomaterials ; 265: 120403, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32980806

RESUMO

Local drug delivery systems, especially hydrogels, show superior strengths in postoperative recurrence prevention. Despite great advances, clinical translation of the hydrogels has been largely restricted as these drug delivery systems generally require chemical modification or additional carrier molecules to form hydrogels, which results in side effects correlative with local inflammation and systemic toxicity. Here, we developed a pure molecular anticancer drug hydrogel that reduced post-surgical tumor recurrence. The macroscopic pure molecular hydrogel was generated via ultrasonication of anticancer drug raltitrexed in aqueous solution, which was facile and environmentally friendly without involving chemical synthesis. Molecular dynamics simulations confirmed that raltitrexed self-assembled into a nanofibrous hydrogel through hydrogen bond and π-π interaction. Delivered as a hydrogel, raltitrexed could effectively decrease tumor recurrence rate and promote the inhibition of tumor growth in vivo. This raltitrexed self-delivery hydrogel has the potential to serve as a powerful auxiliary implement for preventing postoperative local tumor recurrence.

2.
Biomaterials ; 266: 120400, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33022477

RESUMO

It remains a major challenge to develop an effective therapeutic system based on gold nanorods (GNRs) for cancer therapy. Herein, we developed a redox-responsive, in-situ polymerized polyplatinum(IV)-coated gold nanorod (GNR@polyPt(IV)) with coupling of the near-infrared (NIR)-induced hyperthermal effect and redox-triggered drug release in one therapeutic platform as an amplifier of tumor accumulation through mild hyperthermia for enhanced synergistical thermo-chemotherapy. After in-situ polymerized with 2-methacryloyloxy ethyl phosphorylcholine (MPC) and Pt(IV) complex-based prodrug monomer (PPM) onto the surface of GNRs, the nanosized GNR@polyPt(IV) exhibited the advantages of high drug encapsulation efficiency, triggered drug release, and reduced side effect. As demonstrated by thermal imaging and photoacoustic imaging in vitro and in vivo, this GNR@polyPt(IV) exhibited an excellent NIR-associated hyperthermal effect and outstanding capacity of tumor accumulation. Importantly, under a mild hyperthermia process, the vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) were upregulation, resulting in angiogenic vessel around the tumor. Combination with accelerated blood flow and angiogenesis by mild hyperthermia, a dramatic increase of drug accumulation in tumor could be realized after systematic administration. As a result, this amplification fashion of tumor accumulation would contribute the GNR@polyPt(IV) to inhibit tumor progression effectively. Such a facile and simple methodology for enhanced therapeutic effect based on GNRs holds great promises for cancer therapy with further development.

3.
Adv Healthc Mater ; : e2000573, 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33166086

RESUMO

Osteosarcoma is the most primary type of bone tumor occurring in the pediatric and adolescent age groups. In order to obtain the most appropriate prognosis, both tumor recurrence inhibition and bone repair promotion are required. In this study, a ternary nanoscale biomaterial/antitumor drug complex including hydroxyapatite (HA), bovine serum albumin (BSA) and paclitaxel (PTX) is prepared for post-surgical cancer treatment of osteosarcoma in situ. The HA-BSA-PTX nanoparticles, about 55 nm in diameter with drug loading efficiency (32.17 wt%), have sustained release properties of PTX and calcium ions (Ca2+ ) and low cytotoxicity to human fetal osteoblastic (hFOB 1.19) cells in vitro. However, for osteosarcoma (143B) cells, the proliferation, migration, and invasion ability are significantly inhibited. The in situ osteosarcoma model studies demonstrate that HA-BSA-PTX nanoparticles have significant anticancer effects and can effectively inhibit tumor metastasis. Meanwhile, the detection of alkaline phosphatase activity, calcium deposition, and reverse transcription-polymerase chain reaction proves that the HA-BSA-PTX nanoparticles can promote the osteogenic differentiation. Therefore, the HA-BSA-PTX nanodrug delivery system combined with sustained drug release, antitumor, and osteogenesis effects is a promising agent for osteosarcoma adjuvant therapy.

4.
ACS Nano ; 14(10): 13056-13068, 2020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-33016697

RESUMO

Tumor accumulation and intratumoral singlet oxygen (1O2) generation efficiency of photosensitizers (PSs) are two essential factors that determine their photodynamic therapy (PDT) efficacies. How to maximize the PS performance at the tumor site is of great research interest. Herein, we report a metal-organic framework (ZIF-8, ZIF = zeolitic imidazolate framework) assisted in vivo self-assembly nanoplatform, ZIF-8-PMMA-S-S-mPEG, as an effective tool for organic PS payloads to achieve efficient PDT. Using an organic PS with aggregation-induced emission as an example, under intratumoral bioreduction, PS-loaded ZIF-8-PMMA-S-S-mPEG (PS@ZIF-8-PMMA-S-S-mPEG) was self-assembled into large ordered hydrophobic clusters, which greatly enhance tumor retention and accumulation of the PS. Moreover, hydrophobic ZIF-8 assemblies greatly isolate the loaded PSs from water and improve O2 transport for the PSs to effectively produce 1O2 inside tumors under light irradiation. The organic PS is therefore endowed with optimal tumor accumulation and intratumoral 1O2 production, demonstrating the effectiveness of the developed self-assembly strategy in PDT application.

5.
J Control Release ; 328: 425-434, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32889054

RESUMO

MicroRNAs (miRNAs) play crucial roles in maintaining normal physiological processes by regulating gene expression network and thus the tumor-suppressive miRNA has emerged as a promising antitumor agent for cancer treatment. However, targeted delivery of miRNA remains a challenge owing to its intrinsic macromolecular and negatively-charged features. Herein, we first employ the miRNA as crosslinker to construct a nucleic acid nanogel, in which miRNA is embedded and protected inside the three-dimensional (3D) nanostructure. Thereafter, nanobody (Nb) conjugated DNA (Nb-DNA) strands are further loaded on nanogel surface through nucleic acid hybridization, to form a Nb-functionalized nanogel (Nb-nanogel) for tumor-targeted miRNA delivery and antitumor treatment. Both in vitro and in vivo experiments show that nanogel equipped with Nb targeting moieties can greatly promote the miRNA accumulation at the tumor site and cellular uptake efficiency, resulting in significant improvement of the miRNA-mediated antitumor efficacy. This research provides a new approach for targeted miRNA delivery and may pave a new avenue to realize efficient miRNA replacement therapy for cancer treatment.

6.
J Mater Chem B ; 8(36): 8219-8231, 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32803207

RESUMO

Supramolecular block copolymers (SBCs) have received considerable interest in polymer chemistry, materials science, biomedical engineering and nanotechnology owing to their unique structural and functional advantages, such as low cytotoxicity, outstanding biodegradability, smart environmental responsiveness, and so forth. SBCs comprise two or more different homopolymer subunits linked by noncovalent bonds, and these polymers, in particular, combine the dynamically reversible nature of supramolecular polymers with the hierarchical microphase-separated structures of block polymers. A rapidly increasing number of publications on the synthesis and applications of SBCs have been reported in recent years; however, a systematic summary of the design, synthesis, properties and applications of SBCs has not been published. To this end, this review provides a brief overview of the recent advances in SBCs and describes the synthesis strategies, properties and functions, and their widespread applications in drug delivery, gene delivery, protein delivery, bioimaging and so on. In this review, we aim to elucidate the general concepts and structure-property relationships of SBCs, as well as their practical bioapplications, shedding further valuable insights into this emerging research field.

7.
Biomater Sci ; 8(19): 5230-5240, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32845259

RESUMO

Enzymatic biofuel cells (EBFCs), as one of the most promising sustainable and green energy sources, have attracted significant interest. However, the limited lifetime and output power of EBFCs deriving from the intrinsic defects of natural enzyme fail to meet the requirements of commercial applications. As a robust approach, protein engineering shows promising potential to overcome these defects. In this review, we will elaborate on the basic principles, structure and electron transfer pathways of EBFCs, and discuss the strategies of protein engineering for improving the performances of EBFCs. We hope that this review will inspire researchers to envisage efficient enzymes for EBFCs and promote the commercial transformation of EBFCs in implantable medical devices, portable power batteries and even clean-power-driven cars in the near future.

8.
Artigo em Inglês | MEDLINE | ID: mdl-32725869

RESUMO

Molecular imaging has received increased attention worldwide, including in China, because it offers noninvasive characterization of widely diverse clinically significant pathologies. To achieve these goals, nanomedicine has evolved into a broad interdisciplinary field with flexible designs to accommodate and concentrate imaging and therapeutic payloads into pathological cells through selective binding to disease specific cell membrane biomarkers. This concept of personalized medicine reflects the vision of "magic bullets" proposed by German biochemist Paul Ehrlich over 100 years ago. As happening worldwide, Chinese scientists are contributing to this tsunami of science and technologies through impactful national programs and international research collaborations. This review provides a comprehensive update of Chinese innovations to address intractable unmet medical need in China and worldwide in the optical sciences. This article is categorized under: Diagnostic Tools > in vivo Nanodiagnostics and Imaging.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32643224

RESUMO

Combinatorial antitumor therapies using different combinations of drugs and genes are emerging as promising ways to overcome drug resistance, which is a major cause for the failure of cancer treatment. However, dramatic pharmacokinetic differences of drugs greatly impede their combined use in cancer therapy, raising the demand for drug delivery systems (DDSs) for tumor treatment. By employing fluorescent dithiomaleimide (DTM) as a linker, we conjugate two paclitaxel (PTX) molecules with a floxuridine (FdU)-integrated antisense oligonucleotide (termed chemogene) to form a drug-chemogene conjugate. This PTX-chemogene conjugate can self-assemble into a spherical nucleic acid (SNA)-like micellular nanoparticle as a carrier-free DDS, which knocks down the expression of P-glycoprotein and subsequently releases FdU and PTX to exert a synergistic antitumor effect and greatly inhibit tumor growth.

10.
Artigo em Inglês | MEDLINE | ID: mdl-32637366

RESUMO

Vibrios, which include more than 120 valid species, are an abundant and diverse group of bacteria in marine and estuarine environments. Some of these bacteria have been recognized as pathogens of both marine animals and humans, and therefore, their virulence mechanisms have attracted increasing attention. The type III secretion system (T3SS) is an important virulence determinant in many gram-negative bacteria, in which this system directly translocates variable effectors into the host cytosol for the manipulation of the cellular responses. In this study, the distribution of the T3SS gene cluster was first examined in 110 Vibrio strains of 26 different species, including 98 strains isolated from coastal areas in China. Several T3SS1 genes, but not T3SS2 genes (T3SS2α and T3SS2ß), were universally detected in all the strains of four species, Vibrio parahaemolyticus, Vibrio alginolyticus, Vibrio harveyi, and Vibrio campbellii. The effector coding regions within the T3SS1 gene clusters from the T3SS1-positive strains were further analyzed, revealing that variations in the effectors of Vibrio T3SS1 were observed among the four Vibrio species, even between different strains in V. harveyi, according to their genetic organization. Importantly, Afp17, a potential novel effector that may exert a similar function as the known effector VopS in T3SS1-induced cell death, based on cytotoxicity assay results, was found in the effector coding region of the T3SS1 in some V. harveyi and V. campbellii strains. Finally, it was revealed that differences in T3SS1-mediated cytotoxicity were dependent not only on the variations in the effectors of Vibrio T3SS1 but also on the initial adhesion ability to host cells, which is another prerequisite condition. Altogether, our results contribute to the clarification of the diversity of T3SS1 effectors and a better understanding of the differences in cytotoxicity among Vibrio species.

11.
Int J Nanomedicine ; 15: 4691-4703, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32636625

RESUMO

Purpose: Gd-encapsulated carbonaceous dots (Gd@C-dots) have excellent stability and magnetic properties without free Gd leakage, therefore they can be considered as a safe alternative T1 contrast agent to commonly used Gd complexes. To improve their potential for cancer diagnosis and treatment, affibody-modified Gd@C-dots targeting non-small-cell lung cancer (NSCLC) EGFR-positive tumors with enhanced renal clearance were developed and synthesized. Materials and Methods: Gd@C-dots were developed and modified with Ac-Cys-ZEGFR:1907 through EDC/NHS. The size, morphology, and optical properties of the Gd@C-dots and Gd@C-dots-Cys-ZEGFR:1907 were characterized. Targeting ability was evaluated by in vitro and in vivo experiments, respectively. Residual gadolinium concentration in major organs was detected with confocal imaging and inductively coupled plasma mass spectrometry (ICP-MS) ex vivo. H&E staining was used to assess the morphology of these organs. Results: Gd@C-dots with nearly 20 nm in diameter were developed and modified with Ac-Cys-ZEGFR:1907. EGFR expression in HCC827 cells was higher than NCI-H520. In cell uptake assays, EGFR-expressing HCC827 cells exhibited significant MR T1WI signal enhancement when compared to NCI-H520 cells. Cellular uptake of Gd@C-dots-Cys-ZEGFR:1907 was reduced, when Ac-Cys-ZEGFR:1907 was added. In vivo targeting experiments showed that the probe signal was significantly higher in HCC827 than NCI-H520 xenografts at 1 h after injection. In contrast to Gd@C-dots, Gd@C-dots-Cys-ZEGFR:1907 nanoparticles can be efficiently excreted through renal clearance. No morphological changes were observed by H&E staining in the major organs after injection of Gd@C-dots-Cys-ZEGFR:1907. Conclusion: Gd@C-dots-Cys-ZEGFR:1907 is a high-affinity EGFR-targeting probe with efficient renal clearance and is therefore a promising contrast agent for clinical applications such as diagnosis and treatment of NSCLC EGFR-positive malignant tumors.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Meios de Contraste/farmacocinética , Neoplasias Pulmonares/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Pontos Quânticos/química , Animais , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Meios de Contraste/química , Receptores ErbB/metabolismo , Feminino , Gadolínio/química , Gadolínio/farmacocinética , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Neoplasias Pulmonares/patologia , Camundongos Nus , Nanopartículas/química , Distribuição Tecidual , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Artigo em Inglês | MEDLINE | ID: mdl-32686235

RESUMO

Developing non-cationic gene carriers and achieving efficient endo/lysosome escape of functional nucleic acids in cytosol are two major challenges faced by the field of gene delivery. Herein, we demonstrate the concept of self-escape spherical nucleic acid (SNA) to achieve light controlled non-cationic gene delivery with sufficient endo/lysosome escape capacity. In this system, Bcl-2 antisense oligonucleotides (OSAs) were conjugated onto the surface of aggregation-induced emission (AIE) photosensitizer (PS) nanoparticles to form core-shell SNA. Once the SNAs were taken up by tumor cells, and upon light irradiation, the accumulative 1 O2 produced by the AIE PSs ruptured the lysosome structure to promote OSA escape. Prominent in vitro and in vivo results revealed that the AIE-based core-shell SNA could downregulate the anti-apoptosis protein (Bcl-2) and induce tumor cell apoptosis without any transfection reagent.

13.
Biomaterials ; 255: 120071, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32540754

RESUMO

Circulating tumor cells (CTCs) represent the most common way of tumor metastasis and has been considered as a significant index for tumor diagnosis, staging and prognosis. However, CTC detection and analysis are always limited by the scarcity of CTC in the peripheral blood and the interference of blood cells. Therefore, here we presented with a hydrogen peroxide (H2O2)-response nanoprobes with CD44-targeted ability to reduce the interference of blood cells and improve the detection efficiency and accuracy and the pancreatic cancer cell was used to evaluate the feasibility of our probe. Shortly, hydrophobic H2O2-response naphthalimide-borate fluorophore was introduced onto the hydrophilic hyaluronic acid to form an amphiphilic complex, which could self-assemble into fluorescent nanoprobes in water. Our studies demonstrated that the nanoprobes were not only able to specifically recognize the pancreatic cancer cells with overexpressed CD44 proteins and reduce the influence of white blood cells in the peripheral blood, but also capable of semi-quantifying H2O2 content in CTCs, Which could be further used as a significant index for tumor clinical evaluation and therapy.

14.
Chem Commun (Camb) ; 56(54): 7439-7442, 2020 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-32494799

RESUMO

A multitude of maleimides are grafted onto the backbone of a phosphorothioate antisense oligonucleotide (ASO) to generate the construct of maleimide-grafted ASO (Mal-g-ASO). Through click conjugation with cell membrane thiols that triggers endocytosis-independent cellular internalization, Mal-g-ASO exhibited enhanced cellular uptake efficiency, resulting in a remarkable improvement of ASO-based gene silencing.

15.
Nanoscale ; 12(24): 12698-12711, 2020 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-32525189

RESUMO

Nanoparticles (NPs) have been a research focus over the last three decades owing to their unique properties and extensive applications. It is crucial to precisely control the features of NPs including topology, architecture, composition, size, surface and assembly because these features will affect their properties and then applications. Ingenious nanofabrication strategies have been developed to precisely control these features of NPs, especially for templated nanofabrication within predesigned nanoreactors. Compared with conventional nanoreactors (hard templates and supramolecular nanoreactors), unimolecular nanoreactors exhibit (1) covalently stable nanostructures uninfluenced by environmental variations, (2) extensively regulated features of the structure including topology, composition, size, surface and valence due to the rapid development of polymer chemistry, and (3) effective encapsulation of abundant guests with or without strong interaction to achieve the function of loading, delivery and conversion of guests. Thus, unimolecular nanoreactors have shown fascinating prospects as templates for nanofabrication. Various NPs with expected topologies (sphere, rod, tube, branch, and ring), architectures (compact, hollow, core-shell, and necklace-like), compositions (metal, metal oxide, semiconductor, doping, alloy, silica, and composite), sizes (generally 1-100 nm), surface properties (hydrophilic, hydrophobic, reactivity, valence and responsivity) and assemblies (oligomer, chain, and aggregate) can be fabricated easily within reasonably designed unimolecular nanoreactors in a programmable way. In this review, we provide a brief introduction of the properties and types of unimolecular nanoreactors, a condensed summary of representative methodologies of nanofabrication within various unimolecular nanoreactors and a predicted outlook of the potential further developments of this charming nanofabrication approach.

16.
Proc Natl Acad Sci U S A ; 117(21): 11240-11246, 2020 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-32393646

RESUMO

Ice accumulation causes various problems in our daily life for human society. The daunting challenges in ice prevention and removal call for novel efficient antiicing strategies. Recently, photothermal materials have gained attention for creating icephobic surfaces owing to their merits of energy conservation and environmental friendliness. However, it is always challenging to get an ideal photothermal material which is cheap, easily fabricating, and highly photothermally efficient. Here, we demonstrate a low-cost, high-efficiency superhydrophobic photothermal surface, uniquely based on inexpensive commonly seen candle soot. It consists of three components: candle soot, silica shell, and polydimethylsiloxane (PDMS) brushes. The candle soot provides hierarchical nano/microstructures and photothermal ability, the silica shell strengthens the hierarchical candle soot, and the grafted low-surface-energy PDMS brushes endow the surface with superhydrophobicity. Upon illumination under 1 sun, the surface temperature can increase by 53 °C, so that no ice can form at an environmental temperature as low as -50 °C and it can also rapidly melt the accumulated frost and ice in 300 s. The superhydrophobicity enables the melted water to slide away immediately, leaving a clean and dry surface. The surface can also self-clean, which further enhances its effectiveness by removing dust and other contaminants which absorb and scatter sunlight. In addition, after oxygen plasma treatment, the surface can restore superhydrophobicity with sunlight illumination. The presented icephobic surface shows great potential and broad impacts owing to its inexpensive component materials, simplicity, ecofriendliness, and high energy efficiency.

17.
Int J Biol Macromol ; 160: 979-990, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32473217

RESUMO

The degradation effect of ultrasound (US)/hydrogen peroxide (H2O2) on Tremella fuciformis polysaccharide (TFP) were studied. The main process parameters of degradation were evaluated and the structural changes and antioxidant activities of TFP before and after US/H2O2 were analyzed. The results showed that the degradation effect of US/H2O2 was significantly higher than that of US or H2O2 alone, and the degradation of TFP was dependent on the duration of its exposure to US, the ultrasonic amplitude, and the H2O2 and TFP concentrations. US/H2O2 reduced the molecular weight (from 8.14 × 105 Da to 1.27 × 104 Da) and particle size (from 710 nm to 182 nm) of the TFP within 50 min and narrowed its molecular weight and particle size distribution. High performance liquid chromatography, Fourier-transform infrared spectroscopy, Carbon-13 nuclear magnetic resonance, scanning electron microscopy, atomic force microscopy, and Congo red results indicated that the treatment could break down the polysaccharide chains, hinder the aggregation, and improve the conformation flexibility of the TFP molecules without changing the primary structure and monosaccharide composition of TFP. Additionally, the degraded TFPs with low molecular weight exhibited a higher antioxidant activity than the original TFP. These findings suggest that the US/H2O2 treatment is a simple and effective method to prepare a TFP of low molecular weight and high bioactivity.

18.
Int J Biol Macromol ; 156: 354-361, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32298720

RESUMO

A capsular polysaccharides (CPS) producer Bacillus velezensis SN-1 (B. velezensis SN-1) was isolated in Da-jiang, China. We used ultrasonic extraction to obtain CPS from a culture of B. velezensis SN-1 at a yield of 755 mg/L. Using gel permeation chromatography (GPC), CPS was separated into a single peak with a molecular weight of 1.46 × 105 Da. Its structures were characterized by gas chromatography (GC), methylation, Fourier transform infrared spectroscopy (FTIR), and nuclear magnetic resonance (NMR). The CPS was identified as a polysaccharide with a highly branched main chain of mannose with (1 â†’ 3) connections. Moreover, our results revealed that CPS has the capacity to scavenge DPPH radical, hydroxyl radical, ABTS radical and oxygen radical in a manner that relied on concentration. Anti-neoplastic analysis showed that CPS displayed significant anti-tumor activity towards HepG-2 tumor cells. Above findings indicate that CPS generated by B. velezensis SN-1 may be adapted for use as a natural antioxidant in foodstuffs and as an anti-tumor drug.

19.
Int J Biol Macromol ; 157: 36-44, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32339581

RESUMO

An exopolysaccharide (EPS)-producing strain SN-8 isolated from Dajiang was identified as Leuconostoc mesenteroides. When sucrose was used as the carbon source for fermentation, the output of EPS was 2.42 g/L. High performance liquid chromatography analysis confirmed the presence of monomers such as glucan and mannose. The molecular weight detection value is 2.0 × 105 Da. Fourier transform infrared spectroscopy displayed the EPS had the basic skeleton and functional groups of a typical polysaccharide structure. Scanning electron microscopy showed smooth surfaces and compact structure. Thermal performance analysis showed that the highest heat resistance temperature of the EPS was 80 °C. Compared with vitamin C, its hydroxyl radical scavenging rate was as high as 32% and 1,1-diphenyl-2-picrylhydrazyl scavenging rate was as high as 40% under the same concentration. The peanut oil was the most emulsifiable at a concentration of 1.5 mg/mL, and the emulsification index was 0.55. These results might show that the EPS had high application value.

20.
ACS Appl Mater Interfaces ; 12(19): 21441-21449, 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32314901

RESUMO

Considering the high rate of postsurgical tumor recurrence due to the possible residual cancer cells and the non-negligible toxicity of postsurgical systemic chemotherapy, we designed an injectable DNA hydrogel assembled by chemodrug-grafted DNA strands for localized chemotherapy. First, a multitude of camptothecin was successfully grafted on backbones of the phosphorothioate DNAs, which could be assembled into two types of Y-shaped building blocks and then hierarchically associated together to form drug-containing hydrogels. The injectable feature of drug-containing DNA hydrogels enables a minimally invasive approach for local drug administration. Owing to the enzymatic degradation, the hydrogel can gradually disassemble into nanosized particles, allowing its good permeation into the residual tumor tissue and efficient uptake by cells. Together with its sustained and responsive drug release behaviors, the drug-containing DNA hydrogel can significantly inhibit the regrowth of tumor cells and prevent cancer recurrence. Compared to the control groups, mice treated with our drug-containing DNA hydrogel show the lowest tumor relapse rate (1/3) and substantial slow tumor progression. Despite the long-term local embedding, negligible systemic toxicity and organ damages are observed after the treatment with our drug-grafted DNA hydrogel. With excellent antitumor efficacy and low side effects in vivo, our DNA-drug conjugate (DDC)-based hydrogel represents a promising candidate for local adjuvant therapy in cancer treatment.

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