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1.
Adv Healthc Mater ; : e2100896, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34494390

RESUMO

Photodynamic therapy (PDT) has emerged as an attractive alternative in cancer therapy, but therapeutic effects suffer from low photosensitizing efficiency and poor retention of photosensitizes in cancer cells. This paper reports the photosensitizers which show absorption and emission in the long-wavelength region and high photosensitizing efficiency can be formed in situ in cells from 4,6-dibromothieno[3,4-b]thiophene derivative (TT-5-P) after white light irradiation. The self-oligomerization of TT-5-P is uptaken in cells upon light irradiation-induced cell apoptosis simultaneously and efficiently. In addition, the formation of oligomers (TT-5-Ps) enhances the retention time in cells remarkably, which is advantageous for boosting the photodynamic therapy efficiency. Moreover, the selectivity toward tumor cells of TT-5-P can be improved obviously via the formation of complex of TT-5-P with albumin. This in situ photoinduced self-oligomerization strategy can be utilized to design effective biomaterials for long-term imaging and improved therapy.

2.
Biomaterials ; 277: 121115, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34488118

RESUMO

Conductive polymers with high near-infrared absorbance, have attracted considerable attention in the design of intelligent nanomedicines for cancer therapy, especially chemo-photothermal therapy. However, the unknown long-term biosafety of conductive polymers in vivo due to non-degradability hinders their clinic application. Herein, a H2O2-triggered degradable conductive polymer, polyacrylic acid (PAA) stabilized poly(pyrrole-3-COOH) (PAA@PPyCOOH), is fabricated to form nanoparticles with doxorubicin (DOX) for safe and precise chemo-phototherapy. The PAA@PPyCOOH was found to be an ideal photothermal nano-agent with good dispersity, excellent biocompatibility and high photothermal conversion efficiency (56%). After further loading of doxorubicin (DOX), PAA@PPyCOOH@DOX demonstrates outstanding photothermal performance, as well as pH/H2O2 dual-responsive release of DOX in tumors with an acidic and overexpressed H2O2 microenvironment, resulting in superior chemo-photothermal therapeutic effects. The degradation mechanism of PAA@PPyCOOH is proposed to be the ring-opening reaction between the pyrrole-3-COOH unit and H2O2. More importantly, the nanoparticles can be specifically degraded by excess H2O2 in tumor, and the degradation products were confirmed to be excreted via urine and feces. In vivo therapeutic evaluation of chemo-photothermal therapy reveals tumor growth of 4T1 breast cancer model is drastically inhibited and no apparent side-effect is detected, thus indicating substantial potential in clinic application.

3.
J Mater Chem B ; 9(26): 5173-5194, 2021 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-34116565

RESUMO

Platinum drugs are commonly used in cancer therapy, but their therapeutic outcomes have been significantly compromised by the drug resistance of cancer cells. To this end, intensive efforts have been made to develop nanoparticle-based drug delivery systems for platinum drugs, due to their multifunctionality in delivering drugs, in modulating the tumor microenvironment, and in integrating additional genes, proteins, and small molecules to overcome chemoresistance in cancers. To facilitate the clinical application of these promising nanoparticle-based platinum drug delivery systems, this paper summarizes the common mechanisms for chemoresistance towards platinum drugs, the advantages of nanoparticles in drug delivery, and recent strategies of nanoparticle-based platinum drug delivery. Furthermore, we discuss how to design delivery platforms more effectively to overcome chemoresistance in cancers, thereby improving the efficacy of platinum-based chemotherapy.

5.
Nat Biomed Eng ; 5(9): 1048-1058, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34045730

RESUMO

In patients with glioblastoma, resistance to the chemotherapeutic temozolomide (TMZ) limits any survival benefits conferred by the drug. Here we show that the convection-enhanced delivery of nanoparticles containing disulfide bonds (which are cleaved in the reductive environment of the tumour) and encapsulating an oxaliplatin prodrug and a cationic DNA intercalator inhibit the growth of TMZ-resistant cells from patient-derived xenografts, and hinder the progression of TMZ-resistant human glioblastoma tumours in mice without causing any detectable toxicity. Genome-wide RNA profiling and metabolomic analyses of a glioma cell line treated with the cationic intercalator or with TMZ showed substantial differences in the signalling and metabolic pathways altered by each drug. Our findings suggest that the combination of anticancer drugs with distinct mechanisms of action with selective drug release and convection-enhanced delivery may represent a translational strategy for the treatment of TMZ-resistant gliomas.

6.
Dalton Trans ; 50(22): 7715-7724, 2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-33983359

RESUMO

Ru(ii)-based photoactivated chemotherapy (PACT) agents are promising; however, their short wavelength absorption (generally <550 nm) and poor tumor accumulation ability limit their in vivo applications. Herein, bovine serum albumin (BSA) coated lanthanide-doped upconversion nanoparticles (NaYF4:Yb:Tm@NaYF4 (UCNPs)) were loaded with a Ru(ii) PACT agent, i.e. [Ru(dip)2(spc)]+ (dip = 4,7-diphenyl-1,10-phenanthroline; spc = 2-sulfonic acid pyridine-3-carboxylic acid). The resultant UCNP@BSA@Ru can transfer [Ru(dip)2(spc)]+ to tumor cells in vitro as well as tumor tissues in vivo highly efficiently and selectively owing to the targeting ability of BSA and the enhanced permeability and retention effect of the nanoparticles. The subsequent near infrared (NIR) light irradiation at 980 nm or visible light irradiation at 470 nm can initiate dissociation of the spc ligand, and the released Ru(ii) aqua compounds ([Ru(dip)2(H2O)2]2+) may exert a potent cytotoxicity towards a series of cancer cells but a much weaker effect on the normal IOSE80 cells. The in vivo (mouse) results showed that UCNP@BSA@Ru could inhibit tumor growth upon 980 nm irradiation more efficiently than in the dark and more efficiently than cisplatin (in the dark).

7.
Adv Mater ; 33(20): e2100599, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33834553

RESUMO

A systematic combination strategy is proposed for overcoming cisplatin resistance using near-infrared (NIR)-light-triggered hyperthermia. A new photothermal polymer DAP-F is complexed with a reduction-sensitive amphiphilic polymer P1 to form F-NPs with photothermal effect. Subsequently, to build the final nanosystem F-Pt-NPs, F-NPs are combined with Pt-NPs, which are obtained by encapsulating a Pt(IV) prodrug with P1. Mild hyperthermia (43 °C), generated from F-Pt-NPs induced by an 808 nm NIR laser, have various effects such as: i) enhancing the cellular membrane permeability to promote the uptake of drugs; ii) activating cisplatin by accelerating the glutathione consumption; iii) increasing the Pt-DNA adducts formation and possibly the formation of a portion of irreparable Pt-DNA interstrand crosslinks, thereby inhibiting the repair of DNA. In vitro, it is found that even on cisplatin-resistant A549DDP cells, the IC50 of F-Pt-NPs (43 °C) is only 7.0 × 10-6 m Pt mL-1 . In vivo, on a patient-derived xenograft model of multidrug resistant lung cancer, the efficacy of the F-Pt-NPs (43 °C) treatment group shows a tumor inhibition rate of 94%. Taken together, here, an important perspective of resolving cascade drug resistance with the assistance of mild hyperthermia triggered by NIR light is presented, which can be of great significance for clinic translation.

8.
ACS Nano ; 15(3): 5428-5438, 2021 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-33689300

RESUMO

NIR-II (1000-1700 nm) fluorescence imaging is continually attracting strong research interest. However, current NIR-II imaging materials are limited to small molecules with fast blood clearance and inorganic nanomaterials and organic conjugated polymers of poor biodegradability and low biocompatibility. Here, we report a highly biodegradable polyester carrying tandem NIR-II fluorophores as a promising alternative. The polymer encapsulated a platinum intercalator (56MESS, (5,6-dimethyl-1,10-phenanthroline) (1S,2S-diaminocyclohexane) platinum(II)) and was conjugated with both a cell-targeting RGD peptide and a caspase-3 cleavable peptide probe to form nanoparticles for simultaneous NIR-II and apoptosis imaging. In vitro, the nanoparticles were approximately 4-1000- and 1.5-10-fold more potent than cisplatin and 56MESS, respectively. Moreover, in vivo, they significantly inhibited tumor growth on a multidrug-resistant patient-derived mouse model (PDXMDR). Finally, through label-free laser desorption-ionization mass spectrometry imaging (MALDI-MSI), in situ 56MESS release in the deeper tumors was observed. This work highlighted the use of biodegradable NIR-II polymers for monitoring drugs in vivo and therapeutic effect feedback in real-time.


Assuntos
Nanopartículas , Preparações Farmacêuticas , Animais , Linhagem Celular Tumoral , Retroalimentação , Humanos , Camundongos , Polímeros , Resultado do Tratamento
9.
Sci Adv ; 7(13)2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33771859

RESUMO

Various cancers treated with cisplatin almost invariably develop drug resistance that is frequently caused by substantial DNA repair. We searched for acquired vulnerabilities of cisplatin-resistant cancers to identify undiscovered therapy. We herein found that cisplatin resistance of cancer cells comes at a fitness cost of increased intracellular hypoxia. Then, we conceived an inspired strategy to combat the tumor drug resistance by exploiting the increased intracellular hypoxia that occurs as the cells develop drug resistance. Here, we constructed a hypoxia-amplifying DNA repair-inhibiting liposomal nanomedicine (denoted as HYDRI NM), which is formulated from a platinum(IV) prodrug as a building block and payloads of glucose oxidase (GOx) and hypoxia-activatable tirapazamine (TPZ). In studies on clinically relevant models, including patient-derived organoids and patient-derived xenograft tumors, the HYDRI NM is able to effectively suppress the growth of cisplatin-resistant tumors. Thus, this study provides clinical proof of concept for the therapy identified here.

10.
Nano Lett ; 21(8): 3680-3689, 2021 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-33596656

RESUMO

Efficient endosomal escape is the most essential but challenging issue for siRNA drug development. Herein, a series of quaternary ammonium-based amphiphilic triblock polymers harnessing an elaborately tailored pH-sensitive hydrophobic core were synthesized and screened. Upon incubating in an endosomal pH environment (pH 6.5-6.8), mPEG45-P(DPA50-co-DMAEMA56)-PT53 (PDDT, the optimized polymer) nanomicelles (PDDT-Ms) and PDDT-Ms/siRNA polyplexes rapidly disassembled, leading to promoted cytosolic release of internalized siRNA and enhanced silencing activity evident from comprehensive analysis of the colocalization and gene silencing using a lysosomotropic agent (chloroquine) and an endosomal trafficking inhibitor (bafilomycin A1). In addition, PDDT-Ms/siPLK1 dramatically repressed tumor growth in both HepG2-xenograft and highly malignant patient-derived xenograft models. PDDT-Ms-armed siPD-L1 efficiently blocked the interaction of PD-L1 and PD-1 and restored immunological surveillance in CT-26-xenograft murine model. PDDT-Ms/siRNA exhibited ideal safety profiles in these assays. This study provides guidelines for rational design and optimization of block polymers for efficient endosomal escape of internalized siRNA and cancer therapy.


Assuntos
Endossomos , Polímeros , Animais , Linhagem Celular Tumoral , Inativação Gênica , Humanos , Interações Hidrofóbicas e Hidrofílicas , Camundongos , RNA Interferente Pequeno/genética
11.
Soft Matter ; 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33399612

RESUMO

Core/shell PVSt-b-PS@Fe3O4 composite nanoparticles (NPs) are achieved by grafting living cationic block copolymer chains onto the surface of amine-capped Fe3O4 NPs via fast termination. The number of chains grafted can be tuned via the molecular weight of PVSt-b-PS. Upon grafting PEG onto the PVSt block via a click reaction, the resulting (PVSt-g-PEG)-b-PS@Fe3O4 composite NPs become highly dispersible in water. A composite nanoparticle with ten chains is selected as a homogeneous NP to demonstrate the dynamic stepwise organization of the NP as oil is fed into the aqueous dispersion. The individual NPs with captured oil are further aggregated, but remain stable with increasing oil content. Eventually, a Pickering emulsion forms in which the aggregates are anchored at the emulsion interface. This dynamic behavior study helps to provide an understanding of the mechanism by which NPs stabilize Pickering emulsions.

12.
Biomaterials ; 265: 120456, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33099066

RESUMO

External stimuli-responsive nanomedicine with desirable repetitive on-demand drug release character is postulated to greatly accommodate patients' flexible medication regime. To this object, light-activatable liposomes (Pt/Ce6-LP) integrated with both a Ce6 photodynamic component and a tetravalent platinum prodrug (Pt(IV)) chemotherapeutic component are engineered. This multifunctional system was rationally designed using unsaturated phospholipid to achieve repetitive on-demand drug release under discontinuous light irradiation, thus performing chemo-photodynamic therapy effect and immunopotentiation in hypoxic tumor. Furthermore, glutathione (GSH) consumption during transformation from Pt(IV) prodrug to Pt(II) can avoid depletion of reactive oxygen species (ROS) in photodynamic therapy (PDT). Note this positive feedback loop appears to remodel the redox balance of H2O2 and GSH in tumors, alleviating the hypoxic tumor microenvironment. The alleviated hypoxia is found to be critical to the enhancement of PDT efficacy, reversal of cisplatin resistance in tumors, and polarization of tumor-associated macrophages (TAMs) to the immunocompetent M1-phynotype. Pt/Ce6-LP with light radiation demonstrates significant antitumor effect and persistent post-medication inhibition in patient-derived tumor xenograft model of hepatocellular carcinoma.


Assuntos
Lipossomos , Fotoquimioterapia , Linhagem Celular Tumoral , Liberação Controlada de Fármacos , Humanos , Peróxido de Hidrogênio , Hipóxia/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico
13.
ACS Nano ; 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33283501

RESUMO

Excessive oxidative stress in cancer cells can induce cancer cell death. Anticancer activity and drug resistance of chemotherapy are closely related to the redox state of tumor cells. Herein, five lipophilic Pt(IV) prodrugs were synthesized on the basis of the most widely used anticancer drug cisplatin, whose anticancer efficacy and drug resistance are closely related to the intracellular redox state. Subsequently, a series of cisplatin-sensitive and drug-resistant cell lines as well as three patient-derived primary ovarian cancer cells have been selected to screen those prodrugs. To verify if the disruption of redox balance can be combined with these Pt(IV) prodrugs, we then synthesized a polymer with a diselenium bond in the main chain for encapsulating the most effective prodrug to form nanoparticles (NP(Se)s). NP(Se)s can efficiently break the redox balance via simultaneously depleting GSH and augmenting ROS, thereby achieving a synergistic effect with cisplatin. In addition, genome-wide analysis via RNA-seq was employed to provide a comprehensive understanding of the changes in transcriptome and the alterations in redox-related pathways in cells treated with NP(Se)s and cisplatin. Thereafter, patient-derived xenograft models of hepatic carcinoma (PDXHCC) and multidrug-resistant lung cancer (PDXMDR) were established to evaluate the therapeutic effect of NP(Se)s, and a significant antitumor effect was achieved on both models with NP(Se)s. Overall, this study provides a promising strategy to break the redox balance for maximizing the efficacy of platinum-based cancer therapy.

15.
ACS Nano ; 14(11): 14831-14845, 2020 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-33084319

RESUMO

DNA alkylating agents generally kill tumor cells by covalently binding with DNA to form interstrand or intrastrand cross-links. However, in the case of cisplatin, only a few DNA adducts (<1%) are highly toxic irreparable interstrand cross-links. Furthermore, cisplatin is rapidly detoxified by high levels of intracellular thiols such as glutathione (GSH). Since the discovery of its mechanism of action, people have been looking for ways to directly and efficiently remove intracellular GSH and increase interstrand cross-links to improve drug efficacy and overcome resistance, but there has been little breakthrough. Herein, we hypothesized that the anticancer efficiency of cisplatin can be enhanced through iodo-thiol click chemistry mediated GSH depletion and increased formation of DNA interstrand cross-links via mild hyperthermia triggered by near-infrared (NIR) light. This was achieved by preparing an amphiphilic polymer with platinum(IV) (Pt(IV)) prodrugs and pendant iodine atoms (iodides). The polymer was further used to encapsulate IR780 and assembled into Pt-I-IR780 nanoparticles. Induction of mild hyperthermia (43 °C) at the tumor site by NIR light irradiation had three effects: (1) it accelerated the GSH-mediated reduction of Pt(IV) in the polymer main chain to platinum(II) (Pt(II)); (2) it boosted the iodo-thiol substitution click reaction between GSH and iodide, thereby attenuating the GSH-mediated detoxification of cisplatin; (3) it increased the proportion of highly toxic and irreparable Pt-DNA interstrand cross-links. Therefore, we find that mild hyperthermia induced via NIR irradiation can enhance the killing of cancer cells and reduce the tumor burden, thus delivering efficient chemotherapy.


Assuntos
Antineoplásicos , Cisplatino , Reagentes para Ligações Cruzadas , Adutos de DNA , Glutationa , Hipertermia Induzida , Antineoplásicos/farmacologia , Cisplatino/farmacologia , DNA/genética , Humanos
16.
ACS Nano ; 14(10): 13536-13547, 2020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-32924505

RESUMO

Killing tumor cells with a visualized system is a promising strategy in tumor therapy to achieve minimal side effects and high efficiency. Herein, a theranostic nanomedicine (AuNCs-Pt) is developed based on nanocarrier gold nanoclusters (AuNCs) with bifunctions of both NIR-I/NIR-II imaging and glutathione-scavenging abilities. AuNCs-Pt possesses NIR-II imaging capability on a fatal high-grade serous ovarian cancer (HGSOC) model in the deep abdomen, thus facilitating it to be a promising tool for monitoring platinum transportation. Meanwhile, AuNCs-Pt depletes intracellular glutathione to minimize platinum detoxification, effectively maximizing the chemotherapeutic efficacy of platinum. AuNCs-Pt is used to eradicate the tumor burden in this study on a HGSOC model and a patient-derived tumor xenograft model of hepatocellular carcinoma, suggesting great potential for clinical visualized therapy and platinum drug sensitization.


Assuntos
Neoplasias Hepáticas , Nanopartículas Metálicas , Glutationa , Ouro , Humanos , Platina , Nanomedicina Teranóstica
17.
Nanoscale ; 12(36): 18885-18898, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-32902555

RESUMO

Programmed cell death protein-1 (PD-1) on T-cells combined with programmed cell death ligand-1 (PD-L1) critically accounts for tumor immune evasion. Anti-PD-1 (aPD-1) blocks the binding of PD-1 to PD-L1, thus allowing T-cell activation for tumor cell eradication. Currently, the major challenges for cancer immunotherapy are how to improve the response rate and overcome drug resistance. Dermal administration turns out to be a promising route for immunotherapy since skin is a highly active immune organ containing a large population of resident antigen-presenting cells. Microneedle arrays can pierce the immune-cell-rich epidermis, leading to a robust T-cell response in the microenvironment of tumor cells. Herein, we successfully developed a microneedle patch loaded with pH-responsive tumor-targeted lipid nanoparticles (NPs), which allows local delivery of aPD-1 and cisplatin (CDDP) precisely to cancer tissues for cancer therapy. For in vivo studies, aPD-1/CDDP@NPs delivered through microneedles effectively boosted the immune response, thereby a remarkable effect on tumor regression was realized. Synergistic anticancer mechanisms were therefore activated through robust microneedle-induced T-cell response, blockage of PD-1 in T-cells by aPD-1, and an increase in direct cytotoxicity of CDDP in tumor cells. Strikingly, transdermal delivery using MNs increased the response rate in the animal model unresponsive to aPD-1 systemic therapy. This exhibited promise in the treatment of immunotherapy-unresponsive cancers. Taken together, microneedle-mediated local delivery of nano-encapsulated chemotherapeutic and immunotherapeutic agents at tumor skin sites provides a novel treatment strategy and insights into cancer therapy.


Assuntos
Nanopartículas , Neoplasias , Animais , Cisplatino , Imunoterapia , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias/tratamento farmacológico , Microambiente Tumoral
18.
Bioact Mater ; 5(4): 1053-1061, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32691013

RESUMO

mRNA is a novel class of therapeutic modality that holds great promise in vaccination, protein replacement therapy, cancer immunotherapy, immune cell engineering etc. However, optimization of mRNA molecules and efficient in vivo delivery are quite important but challenging for its broad application. Here we present an ionizable lipid nanoparticle (iLNP) based on iBL0713 lipid for in vitro and in vivo expression of desired proteins using codon-optimized mRNAs. mRNAs encoding luciferase or erythropoietin (EPO) were prepared by in vitro transcription and formulated with proposed iLNP, to form iLP171/mRNA formulations. It was revealed that both luciferase and EPO proteins were successfully expressed by human hepatocellular carcinoma cells and hepatocytes. The maximum amount of protein expression was found at 6 h post-administration. The expression efficiency of EPO with codon-optimized mRNA was significantly higher than that of unoptimized mRNA. Moreover, no toxicity or immunogenicity was observed for these mRNA formulations. Therefore, our study provides a useful and promising platform for mRNA therapeutic development.

19.
Chem Commun (Camb) ; 56(65): 9344-9347, 2020 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-32672289

RESUMO

A clustered Nb-drug conjugate (cNDC@PEG) was designed using anti-EGFR Nb to specifically deliver Pt(iv) prodrugs to tumors. cNDC@PEG efficiently targets EGFR positive tumor cells, and the clustered cNDC@PEG is more efficient in inhibiting tumor growth in vivo than the monomeric NDC. This work provides a novel strategy for the construction of a multi-valent NDC using dendrimers.


Assuntos
Antineoplásicos/farmacologia , Nanopartículas/química , Neoplasias/tratamento farmacológico , Compostos Organoplatínicos/farmacologia , Polietilenoglicóis/química , Pró-Fármacos/farmacologia , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Portadores de Fármacos/química , Humanos , Camundongos , Neoplasias/patologia , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Compostos Organoplatínicos/química , Pró-Fármacos/química
20.
Dalton Trans ; 49(24): 8107-8113, 2020 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-32490446

RESUMO

Cisplatin is a platinum-based chemotherapeutic agent widely used in the treatment of various solid tumors. However, a major challenge in the use of cisplatin and in the development of cisplatin derivatives, namely Pt(iv) prodrugs, is their premature reduction in the bloodstream before reaching cancer cells. To circumvent this problem, we designed liposomal nanoparticles coupled with a cholesterol-tethered amphiphilic Pt(iv) prodrug. The addition of cholesterol served to stabilize the formation of the liposome, while selectively incorporating cholesterol as the axial ligand also allowed the Pt(iv) prodrug to readily migrate into the liposomal bilayer. Notably, upon embedding into the nanoparticles, the Pt(iv) prodrug showed marked resistance against premature reduction in human plasma in vitro. Pharmacokinetic analysis in a mouse model also showed that the nanoparticles significantly extend the half-life of the Pt(iv) prodrug to 180 min, which represents a >6-fold increase compared to cisplatin. Importantly, such lipid modification did not compromise the genotoxicity of cisplatin, as the Pt(iv) prodrug induced DNA damage and apoptosis in ovarian cancer cell lines efficiently. Taken together, our strategy provides a novel insight as to how to stabilize a platinum-based compound to increase the circulation time in vivo, which is expected to enhance the efficacy of drug treatment.


Assuntos
Antineoplásicos/farmacologia , Nanopartículas/química , Compostos Organoplatínicos/farmacologia , Pró-Fármacos/farmacologia , Tensoativos/farmacologia , Antineoplásicos/sangue , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Colesterol/sangue , Colesterol/química , Colesterol/farmacologia , Cisplatino/sangue , Cisplatino/química , Cisplatino/farmacologia , Dano ao DNA , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Lipossomos/sangue , Lipossomos/química , Estrutura Molecular , Nanopartículas/metabolismo , Compostos Organoplatínicos/sangue , Compostos Organoplatínicos/química , Pró-Fármacos/química , Pró-Fármacos/metabolismo , Relação Estrutura-Atividade , Tensoativos/química , Tensoativos/metabolismo , Fatores de Tempo , Células Tumorais Cultivadas
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