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1.
Artigo em Inglês | MEDLINE | ID: mdl-31603313

RESUMO

Herein, we construct a structure-switchable gemcitabine (Ge)-containing DNA nanogel that can respond to the intracellular acidic environment, subsequently facilitating the chemodrug release inside the cells. Based on the structural similarity between Ge and deoxycytidine (dC), dC nucleotides in the component DNA strands used for nanogel assembly are fully replaced by Ge during their synthesis. By changing the designed sequences, two Ge-containing Y-shaped motifs with different sticky ends are first assembled and then associated together to form nanogel by sticky-end hybridizations. In particular, one of the sticky-end sequences is arbitrarily designed to be rich of Ge and the other is designed to be partially complementary to the first Ge-rich sticky end. At the neutral or basic condition, the Ge-rich sticky ends hybridize with the partially complementary sticky ends on the second Y motifs, keeping the assembled nanogel stable. Upon being exposed to the acidic condition, Ge-rich sticky ends intend to form intramolecular i-motif-like quadruplex structures, resulting in the disassembly of the nanogel. On the one hand, the nanosized feature enables the Ge-containing nanogel with rapid cellular uptake behavior. On the other hand, the pH-responsive feature endows the rapid disassembly of the nanogel to facilitate the enzymatic drug release inside the cell, resulting in the enhanced anticancer activity of the DNA-based drug delivery system.

2.
Small ; : e1903208, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31617295

RESUMO

Cervical cancer treatment is subject to limited drug access to locally diseased targets and generally resistant to chemotherapy, thus it is essential to develop a local drug delivery system to overcome these problems, premised on guaranteeing drug efficacy. With this goal in mind, a multivalent interactions-based mucoadhesive nanogel for vaginal delivery is proposed. Briefly, the nanogel is constructed with mucoadhesive poly(acrylic acid) as the backbone and multiple inclusions between ß-cyclodextrin and paclitaxel as the crosslinking points. The in vitro experiments demonstrate that nanogel exerts high cytotoxicity to cancer cells, reverses multidrug resistance effectively, and successfully promotes the permeation of drugs. More to the point, as proved in the in vivo experiments, the retention time in the vagina is prolonged and the tumor growth is effectively suppressed by the nanogel without any side effects in the orthotopic cervical cancer model. As mentioned above, this novel mucoadhesive nanogel is believed to be a useful tool toward designing drug delivery systems for cervical cancer treatment.

3.
Nanoscale ; 11(37): 17211-17215, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31531437

RESUMO

Herein, we report a non-cationic DNA-crosslinked nanogel for intracellular delivery of a Cas9 and single guide RNA (Cas9/sgRNA) complex. A DNA-grafted polycaprolactone brush (DNA-g-PCL) is first loaded with the Cas9/sgRNA complex and then crosslinked by DNA linkers via nucleic acid hybridization to form a nanosized hydrogel, in which the gene editing tools are embedded and protected inside. With compact architecture, the Cas9/sgRNA complex-containing nanogel exhibited excellent physiological stability against nuclease digestion and enhanced cellular uptake efficiency, making the delivery system a promising tool for target genome editing.

4.
Biomater Sci ; 7(8): 3489-3496, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31282916

RESUMO

Although nanodrugs have been shown to evade P-glycoprotein (P-gp) recognition and reverse multi-drug resistance (MDR) in cancer, a specific mechanism of how nanodrugs reverse MDR is still unclear. Herein, we investigate the underlying MDR reversal mechanism by studying the in vitro behaviors of model nanodrugs, including internalization, intracellular drug release and intracellular drug enrichment. Comprehensive experimental results showed that the internalization process of nanodrugs can change the distribution of P-gp in MDR cells and significantly reduce the P-gp level in the cell membrane, which might be the key step for MDR reversal. This work offers novel mechanistic insights into MDR reversal by nanodrugs, and this process involves reducing the P-gp distribution ratio in the cell membrane through unique cell internalization behavior rather than merely evading P-gp recognition. Moreover, we further demonstrated that the MDR reversal capacity of nanodrugs follows a size-dependent pattern.

5.
Angew Chem Int Ed Engl ; 58(39): 13794-13798, 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31328376

RESUMO

Most chemotherapeutics are hydrophobic molecules and need to be converted into hydrophilic form before administration. Based on the excellent hydrophilicity and programmability of DNA, now, a general strategy to construct a precise drug-containing DNA framework for cancer treatment is reported. In this novel drug delivery system, carbonethyl bromide-modified camptothecin (CPT) is employed to directly react with phosphorothioate (PS) modified DNAs, resulting in the formation of chemotherapeutics-grafted DNAs with a responsive disulfide linkage. By tuning the number and site of PS modifications on DNA strands, hydrophilicity of the obtained DNA-drug conjugates (DDCs) can be regulated to retain their aqueous solubility and capability of molecular recognition. Subsequently, programmable DNA nanotechnology enables the self-assembly of a precise drug-containing tetrahedral framework with stimuli-responsive feature and enhanced antitumor efficacy both in vitro and in vivo.

6.
J Nanosci Nanotechnol ; 19(12): 7551-7556, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31196260

RESUMO

Cardiovascular disease is an important problem in developed countries and the effective target of treatment should be further developed. ETB receptor is one of receptor of ET system, which may affect the function of vascular smooth muscle cell via NO released. In order to clarify the theory, we had cell culture with or without ET-1 treatment. Flow cytometry had been used to prove cell apoptosis and transwell assay had been used to detect the ability of cell migration. The expression of ET-1, ICAM-1, VCAM-1, MMP-9 and CRP were detected by using qRT-PCR and Western blot assay. After we had found that RES-701-1 one of ETB receptor antagonists can induced VSMC apoptosis and migration. Also RES-701-1 can down regulated ICAM-1, VCAM-1, MMP-9 and CRP while ET-1 was the opposite. In a conclusion ETB receptor is one of the role target to mediate vascular smooth muscle cell through the ET system and it may be a significant treating target in cardiovascular disease in the future.

7.
Theranostics ; 9(11): 3293-3307, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31244955

RESUMO

The noninvasive nature of photodynamic therapy (PDT) enables the preservation of organ function in cancer patients. However, PDT is impeded by hypoxia in the tumor microenvironment (TME) caused by high intracellular oxygen (O2) consumption and distorted tumor blood vessels. Therefore, increasing oxygen generation in the TME would be a promising methodology for enhancing PDT. Herein, we proposed a concept of ferroptosis-promoted PDT based on the biochemical characteristics of cellular ferroptosis, which improved the PDT efficacy significantly by producing reactive oxygen species (ROS) and supplying O2 sustainably through the Fenton reaction. In contrast to traditional strategies that increase O2 based on decomposition of limited concentration of hydrogen peroxide (H2O2), our methodology could maintain the concentration of H2O2 and O2 through the Fenton reaction. Methods: For its association with sensitivity to ferroptosis, solute carrier family 7 member 11 (SLC7A11) expression was characterized by bioinformatics analysis and immunohistochemistry of oral tongue squamous cell carcinoma (OTSCC) specimens. Afterwards, the photosensitizer chlorin e6 (Ce6) and the ferroptosis inducer erastin were self-assembled into a novel supramolecular Ce6-erastin nanodrug through hydrogen bonding and π-π stacking. Then, the obtained Ce6-erastin was extensively characterized and its anti-tumor efficacy towards OTSCC was evaluated both in vitro and in vivo. Results: SLC7A11 expression is found to be upregulated in OTSCC, which is a potential target for ferroptosis-mediated OTSCC treatment. Ce6-erastin nanoparticles exhibited low cytotoxicity to normal tissues. More significantly, The over-accumulated intracellular ROS, increased O2 concentration and inhibited SLC7A11 expression lead to enhanced toxicity to CAL-27 cells and satisfactory antitumor effects to xenograft tumour mouse model upon irradiation. Conclusion: Our ferroptosis promoted PDT approach markedly enhances anticancer actions by relieving hypoxia and promoting ROS production, thereby our work provides a new approach for overcoming hypoxia-associated resistance of PDT in cancer treatment.

8.
Angew Chem Int Ed Engl ; 58(26): 8719-8723, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31095853

RESUMO

Exosomal microRNAs (miRNAs) are important biomarkers for clinical diagnosis and disease treatment monitoring. However, most approaches for exosomal miRNA detection are time-consuming, laborious, and expensive. Herein, we report a virus-mimicking fusogenic vesicle (Vir-FV) that enables rapid, efficient, and high-throughput detection of exosomal miRNAs within 2 h. Fusogenic proteins on Vir-FVs can specifically target the sialic-acid-containing receptors on exosomes, inducing efficient fusion of Vir-FVs and exosomes. Upon vesicle content mixing, the molecular beacons encapsulated in Vir-FVs specifically hybridize with the target miRNAs in the exosomes, generating fluorescence. Combined with flow cytometry, the Vir-FVs can not only detect exosomal miRNAs but also distinguish tumor exosomes from normal exosomes by sensing the tumor-related miRNAs, paving the way towards the rapid and efficient detection of exosomal miRNAs for diagnosis and prognosis prediction of diseases.

9.
Biomaterials ; 211: 68-80, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31096162

RESUMO

Up to now, limited tumor penetration and poor therapeutic efficiency of drug-loaded nanoparticles are still the major challenges in nanomedicines for cancer chemotherapy. In photodynamic therapy, photosensitizers are often used to generate cytotoxic reactive oxygen species to kill cancer cells. Here, we report a kind of ROS-responsive nanoparticles with light-triggered size-reducing for enhanced tumor penetration and in vivo drug delivery to improve therapeutic efficiency. The nanoparticles were constructed by the self-assembly of an amphiphilic hyperbranched polyphosphoester containing thioketal units and photosensitizers, which is synthesized through the self-condensing ring-opening polymerization of a novel cyclic phosphate monomer and then end-capped with photosensitizer Chlorin e6. These nanoparticles have an initial averaged diameter of ∼210 nm, which can be used as drug carriers to load camptothecin with relatively stable in blood circulation. The CPT-loaded nanoparticles can be concentrated in tumor tissues through the long blood circulation and enhanced permeability and retention effect. Upon 660 nm laser irradiation on tumor tissues, the Ce6s in nanoparticles can effectively generate ROS to kill cancer cells meanwhile cleave the thioketal units to sequentially reduce the size of nanoparticles, which facilitate them more efficient tumor penetration with a programmable release of CPT. Both in vitro and in vivo studies confirmed the above results. Such ROS-responsive nanoparticles with light-triggered size-reducing provided a feasible approach to improve drug tumor penetration and achieve satisfied therapeutic efficacy.

10.
Chem Commun (Camb) ; 55(46): 6603-6606, 2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31119252
11.
Chem Commun (Camb) ; 55(47): 6735-6738, 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31119236

RESUMO

A near-infrared (NIR)-sensitive gated assembly of supramolecular conjugated unimicelles based on robust host-guest recognition between a ß-cyclodextrin-grafted hyperbranched conjugated polymer and azobenzene-functionalized poly(ethylene glycol) was constructed. Utilized as a drug carrier, these unimicelles exhibited controlled drug release through the NIR-triggered photoisomerization of azobenzene in cancer cells via a two-photon excited fluorescence resonance energy transfer (TP-FRET) approach, leading to efficient cancer therapy.


Assuntos
Doxorrubicina/metabolismo , Portadores de Fármacos/química , Raios Infravermelhos , Micelas , Compostos Azo/química , Doxorrubicina/química , Liberação Controlada de Fármacos , Transferência Ressonante de Energia de Fluorescência , Células HeLa , Humanos , Isomerismo , Microscopia Confocal , Fótons , Polietilenoglicóis/química , Polímeros/química , beta-Ciclodextrinas/química
12.
J Am Chem Soc ; 141(17): 6955-6966, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30964284

RESUMO

Combinatorial chemo and gene therapy provides a promising way to cure drug-resistant cancer, since the codelivered functional nucleic acids can regulate drug resistance genes, thus restoring sensitivity of the cells to chemotherapeutics. However, the dramatic chemical and physical differences between chemotherapeutics and nucleic acids greatly hinder the design and construction of an ideal drug delivery system (DDS) to achieve synergistic antitumor effects. Herein, we report a novel approach to synthesize a nanosized DDS using drug-integrated DNA with antisense sequences (termed "chemogene") to treat drug-resistant cancer. As a proof of concept, floxuridine (F), a typical nucleoside analog antitumor drug, was incorporated in the antisense sequence in the place of thymine (T) based on their structural similarity. After conjugation with polycaprolactone, a spherical nucleic acid (SNA)-like two-in-one chemogene can be self-assembled, which possesses the capabilities of rapid cell entry without the need for a transfection agent, efficient downregulation of drug resistance genes, and chronic release of chemotherapeutics for treating the drug-resistant tumors in both subcutaneous and orthotopic liver transplantation mouse models.

13.
Chem Commun (Camb) ; 55(29): 4222-4225, 2019 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-30896698

RESUMO

DNA tetrahedra are employed as building blocks to construct a novel DNA-based nanogel for intracellular siRNA delivery. With a compact architecture that embeds functional siRNA inside, the self-assembled nanogel can efficiently enter cells and knock down the target gene expression, making them potential noncationic vectors for functional nucleic acid delivery.


Assuntos
DNA/química , Portadores de Fármacos/química , Inativação Gênica , Nanopartículas/química , Nanoestruturas/química , RNA Interferente Pequeno/química , RNA Interferente Pequeno/genética , Géis , Células HeLa , Humanos , Espaço Intracelular/metabolismo , RNA Interferente Pequeno/metabolismo
14.
Biomater Sci ; 7(6): 2421-2429, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-30924484

RESUMO

The ß-barrel structure of green fluorescent protein (GFP) provides a confined environment to enhance its fluorescence efficiency. Inspired by the unique structure of GFP, we reported a self-restricted GFP chromophore analogue which was rationally grafted onto the middle or the terminal of poly(ethylene glycol)-block-poly(N-isopropyl acrylamide) (PEG-b-PNIPAM) via click chemistry to obtain PEG-GA-PNIPAM and PEG-PNIPAM-GA (GA: MeOBDPI). These structures were characterized through NMR, GPC, and FT-IR. By varying the length of PNIPAM and the location of the GFP chromophore, self-assembly behaviour and fluorescence intensity were correspondingly changed. PEG-GA-PNIPAM and PEG-PNIPAM-GA were assembled into nano-sized spherical micelles above the low critical solution temperature (LCST). The size of the micelles increased with the length of the PNIPAM block. These optical properties were carefully evaluated by UV-Vis and fluorescence spectroscopy. The results indicated that increasing the length of the PNIPAM block enhanced the fluorescence in water, and PEG-PNIPAM74-GA has more remarkable fluorescence intensity than PEG-GA-PNIPAM106 in living cells such as MCF-7 cells. Furthermore, the fluorescence behaviour of PEG-PNIPAM74-GA was studied in MCF-7 cells and L929 cells. The result showed that PEG-PNIPAM74-GA was mostly located in the cytoplasm. Compared with the CellTracker™ Red CMTPX dye, it could enter into MCF-7 cells and L929 cells more easily in DMEM with 10% FBS. Therefore, PEG-PNIPAM74-GA has potential application prospects for living cell imaging.

15.
Adv Mater ; 31(16): e1807533, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30847970

RESUMO

To stress the role of deoxyribonucleic acid (DNA) as a drug carrier, an efficient conjugation strategy in which chemotherapeutics can be grafted onto a phosphorothiolated DNA backbone through the reaction between the phosphorothioate group (PS) and a benzyl bromide group is proposed. As a proof of concept, benzyl-bromide-modified paclitaxel (PTX) is employed to graft onto the DNA backbone at the PS modification sites. Due to the easy preparation of phosphorothiolated DNA at any desired position during its solid-phase synthesis, diblock DNA strands containing both normal phosphodiester segment (PO DNA) and phosphorothiolate segment (PS DNA) are directly grafted with a multitude of PTXs without using complicated and exogenous linkers. Then, the resulting amphiphilic PO DNA-blocked-(PS DNA-grafted PTX) conjugates (PO DNA-b-(PS DNA-g-PTX)) assemble into PTX-loaded spherical nucleic acid (SNA)-like micellar nanoparticles (PTX-SNAs) with a high drug loading ratio up to ≈53%. Importantly, the PO DNA segment maintains its molecular recognition property and biological functions, which allows the as-prepared PTX-SNAs to be further functionalized with tumor-targeting aptamers, fluorescent probe strands, or antisense sequences. These multifunctional PTX-SNAs demonstrate active tumor-targeting delivery, efficient inhibition of tumor growth, and the reversal of drug resistance both in vitro and in vivo for comprehensive antitumor therapy.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , DNA/química , Portadores de Fármacos/química , Paclitaxel/administração & dosagem , Oligonucleotídeos Fosforotioatos/química , Animais , Aptâmeros de Nucleotídeos/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Liberação Controlada de Fármacos , Resistencia a Medicamentos Antineoplásicos , Corantes Fluorescentes/química , Humanos , Camundongos Nus , Micelas , Nanopartículas/química
16.
J Ultrasound Med ; 38(9): 2417-2425, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30680779

RESUMO

OBJECTIVE: This study aimed to compare the efficacy of Sonazoid and SonoVue in subjects with focal liver lesions. METHODS: The patients who had untreated focal solid liver lesions confirmed by B-mode ultrasonography were eligible for the study. The target lesion and whole liver were scanned by gray scale ultrasonography; then, contrast-enhanced ultrasonography was performed, and the results were evaluated blindly. The main end point was accuracy improvement with postcontrast versus precontrast ultrasound examination for diagnosis of the target lesion of interest as malignant or benign against the reference standard. RESULTS: There were 65 patients with 65 hepatic tumors enrolled in the study. The improvement of diagnostic accuracy was 0.30 in the Sonazoid group and 0.16 in the SonoVue group (95% confidence interval, -0.828-0.168; P = .24). Using 20% as the noninferiority margin, the upper limit of the 95% confidence interval (0.168) was less than 0.20. The number of lesions detected during the whole-liver scanning in the Sonazoid group was significantly more than that detected in the SonoVue group (P = .024). CONCLUSION: The diagnosis value of Sonazoid is noninferior to SonoVue, and this new contrast agent can improves the whole-liver image quality.

17.
Biomater Sci ; 2018 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-30474655

RESUMO

Cationic gelatin nanoparticles ((+)nGNPs) were prepared by in situ polymerization upon the surfaces of monodispersed gelatin nanoparticles (GNPs) using N-(3-Aminopropyl)methacrylamide (APm) as monomer, which were then decorated with doxorubicin terminated poly(2-methylacryloyloxyethyl phosphorylcholine) (DOX-pMPC) via EDC/NHS conjugation to obtain core-shell nanoparticles ((+)nGNPs@DOX-pMPC) for cancer therapy. The non-fouling pMPC shell could effectively shield the positively charged surface of inner nanoparticle and prevent non-specific protein adsorption, thus endowing the materials with potential for long-acting cancer treatment. Furthermore, the acyl hydrazone bond connecting DOX and pMPC chain could be easily hydrolyzed in the weakly acidic tumor microenvironment. After decladding of the pMPC shell, electropositive (+)nGNPs carrying the drugs can be effectively internalized by cancer cells to induce apoptosis, avoiding undesirable hindrance caused by the superhydrophilic outer layer. On combining the above properties, this drug delivery system can be a promising candidate for long-acting, low-toxicity and high-efficiency cancer therapy.

18.
Biomater Sci ; 6(11): 2896-2904, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30209472

RESUMO

Polyethylene glycol (PEG) is widely used in the biomedical field due to its outstanding properties. There are plenty of reports on the safety of PEG, but they are mostly restricted to its pharmacokinetic behaviour and pathological effect in vivo, and fail to elucidate its biological effects on cells at the molecular level. Consequently, here we illuminate the biological effect of PEG on a specific cellular pathway. We found that PEG could induce short-term urea cycle inhibition in rat liver cells in vitro without damaging the mitochondria and cells, which was proven to be an adaptive and reversible response to PEG at the molecular level. PEG could also induce a transient hepatic stress response in vivo, which was closely related with the urea cycle disorder. As a mechanistic study on the interactions between a synthetic biomedical polymer and cells at the molecular level, our work provides novel insights into the biological effects of polymers on a cellular system and is fundamental to the development of biomedical polymers.

19.
ACS Appl Mater Interfaces ; 10(31): 26005-26015, 2018 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-30001103

RESUMO

Glucose oxidase (GOx) has seen large-scale technological applications, and the determinations of its activity that is directly related to the enzymatic functions are extremely important. However, conventional methods to analyze the enzymatic activity involving high oxygen dependency and indirect redox reactions are usually tedious and restricted in complicated environments. For analyzing enzymatic activity by direct detection of the electron signals from the active centers, mediators are often used for facilitating the electron transfer. Differing from common methods of preparing electron mediators-contained GOx composites, a strategy aiming at remolding of the enzyme itself has been proposed in this work. Cofactor-like molecule 2'-diallyamino-ethyl flavin (DAA-flavin) derived from riboflavin is synthesized and incorporated as cross-linker into the polyacrylamide (PAAm) network around GOx surface by in situ polymerization to obtain enzyme nanocapsules termed as GOx@Fla-c-PAAm. The peripheral polymer shell confines the orientation of GOx and prevents it from denaturing, whereas incorporated DAA-flavin can replace the oxygen as an alternative electron acceptor to interact with the active centers of GOx in the presence of the substrate, thus giving the nanocapsules oxygen-independent characteristics. The introduced unlimited cofactor-like molecules endow the nanocapsules redox-related fluorescence, and the intensity variation is closely correlated with the enzymatic activity. There is a high goodness of fitting ( R2 ∼ 0.990) between the slope of linear fluorescence-time plots and enzymatic activity, thereby making the nanocapsules a reliable activity-reporting enzymatic nanosystem with oxygen-independent fluorescence variation for further extended potential application in biofuel cells and biosensors.

20.
Biomater Sci ; 6(8): 2261-2269, 2018 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-29999073

RESUMO

Multidrug resistance (MDR) is one of the most important reasons for the failure of clinical chemotherapy treatment of cancer patients. Although several strategies have been proposed to overcome MDR, their contributions in improving therapeutic efficacy are not adequate. Herein, we constructed a nano-twindrug using a supramolecular self-assembling strategy, with the aim of efficiently reversing MDR. Due to the supramolecular interactions, doxorubicin (DOX) and vorinostat (SAHA) could self-assemble into stable spherical nanoparticles with a size of ∼160 nm. Since the antitumor drugs were not modified by nontherapeutic drug carriers, our strategy ensured a drug-loading efficacy of 100%. Furthermore, our study revealed that the DOX-SAHA nano-twin drug could enter drug-resistant cancer cells and inhibit their proliferation more effectively in vitro than single DOX, SAHA, or a DOX/SAHA mixture. In the meantime, the DOX-SAHA nano-twin drug could accumulate at the tumor site in vivo and show higher antitumor efficacy accompanied by low side effects.


Assuntos
Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Nanopartículas/química , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Doxorrubicina/síntese química , Doxorrubicina/química , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Células MCF-7 , Substâncias Macromoleculares/síntese química , Substâncias Macromoleculares/química , Substâncias Macromoleculares/farmacologia , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Estrutura Molecular , Espécies Reativas de Oxigênio/análise , Espécies Reativas de Oxigênio/metabolismo , Células Tumorais Cultivadas
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