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1.
World J Psychiatry ; 14(6): 812-821, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38984333

RESUMO

BACKGROUND: Psychological problems are becoming increasingly prominent among older patients with leukemia, with patients potentially facing stigmatization after diagnosis. However, there is limited research on the stigma experienced by these patients and the factors that may contribute to it. AIM: To investigate the stigma faced by older patients after being diagnosed with leukemia and to analyze the potential influencing factors. METHODS: A retrospective analysis was conducted using clinical data obtained from questionnaire surveys, interviews, and the medical records of older patients with leukemia admitted to the Hengyang Medical School from June 2020 to June 2023. The data obtained included participants' basic demographic information, medical history, leukemia type, family history of leukemia, average monthly family income, pension, and tendency to conceal illness. The Chinese versions of the Social Impact Scale (SIS), Perceived Social Support Scale (PSSS), Self-Rating Anxiety Scale (SAS), and Self-Rating Depression Scale (SDS) were used to assess indicators related to stigma, social support, and mental health status. We used Pearson's correlation coefficient to analyze the strength and direction of the relationship between the scores of each scale, and regression analysis to explore the factors related to the stigma of older patients with leukemia after diagnosis. RESULTS: Data from 120 patients with leukemia aged 65-80 years were analyzed. The total score on the SIS and PSSS was 43.60 ± 4.07 and 37.06 ± 2.87, respectively. The SAS score was 58.35 ± 8.32 and the SDS score was 60.58 ± 5.97. The stigma experienced by older leukemia patients was negatively correlated with social support (r = -0.691, P < 0.05) and positively correlated with anxiety and depression (r = 0.506, 0.382, P < 0.05). Age, education level, smoking status, average monthly family income, pension, and tendency to conceal illness were significantly associated with the participants' level of stigma (P < 0.05). Age, smoking status, social support, anxiety, and depression were predictive factors of stigmatization among older leukemia patients after diagnosis (all P < 0.05), with a coefficient of determination (R2) of 0.644 and an adjusted R2 of 0.607. CONCLUSION: Older patients commonly experience stigmatization after being diagnosed with leukemia. Factors such as age, smoking status, social support, and psychological well-being may influence older patients' reported experience of stigma.

2.
ACS Appl Mater Interfaces ; 15(33): 39064-39080, 2023 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-37523857

RESUMO

No current pharmacological approach is capable of simultaneously inhibiting the symptomatology and structural progression of osteoarthritis. M1 macrophages and activated synovial fibroblasts (SFs) mutually contribute to the propagation of joint pain and cartilage destruction in osteoarthritis. Here, we report the engineering of an apoptotic neutrophil membrane-camouflaged liposome (termed "NM@Lip") for precise delivery of triamcinolone acetonide (TA) by dually targeting M1 macrophages and activated SFs in osteoarthritic joints. NM@Lip has a high cellular uptake in M1 macrophages and activated SFs. Furthermore, TA-loaded NM@Lip (TA-NM@Lip) effectively repolarizes M1 macrophages to the M2 phenotype and transforms pathological SFs to the deactivated phenotype by inhibiting the PI3K/Akt pathway. NM@Lip retains in the joint for up to 28 days and selectively distributes into M1 macrophages and activated SFs in synovium with low distribution in cartilage. TA-NM@Lip decreases the levels of pro-inflammatory cytokines, chemokines, and cartilage-degrading enzymes in osteoarthritic joints. In a rodent model of osteoarthritis-related pain, a single intra-articular TA-NM@Lip injection attenuates synovitis effectively and achieves complete pain relief with long-lasting effects. In a rodent model of osteoarthritis-related joint degeneration, repeated intra-articular TA-NM@Lip injections induce no obvious cartilage damage and effectively attenuate cartilage degeneration. Taken together, TA-NM@Lip represents a promising nanotherapeutic approach for osteoarthritis therapy.


Assuntos
Lipossomos , Osteoartrite , Humanos , Lipossomos/metabolismo , Neutrófilos/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Osteoartrite/patologia , Macrófagos , Fibroblastos/metabolismo , Dor/metabolismo
3.
Acta Biomater ; 146: 357-369, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35577045

RESUMO

Photodynamic therapy (PDT) is an emerging therapeutic approach that can inhibit tumor growth by destroying local tumors and activating systemic antitumor immune responses. However, PDT can be ineffective because of photosensitizer aggregation, tumor-induced dendritic cells (DCS) dysfunction and PDT-mediated immunosuppression. Therefore, we designed chondroitin sulfate-based prodrug nanoparticles for the co-delivery of the photosensitizer chlorin e6 (Ce6) and retinoic acid (RA), which can reduce PDT-mediated immunosuppression by disrupting the Golgi apparatus and blocking the production of immunosuppressive cytokines. Moreover, CpG oligodeoxynucleotide was combined as immunoadjuvant to promote the maturation of DCs. As expected, the strategy of Golgi apparatus targeting immunotherapy combined PDT was confirmed to relieve PDT-induced immunosuppression, showed excellent PDT antitumor efficacy in B16F10-subcutaneous bearing mice model. Thus, our finding offers a promising approach for photodynamic immunotherapy of advanced cancers. STATEMENT OF SIGNIFICANCE: Golgi apparatus has been shown to be a potential target of immunosuppression for producing several immunosuppressive cytokines. In this work, a Golgi apparatus-targeted prodrug nanoparticle was developed to enhance the immune response in photodynamic immunotherapy. The nanoparticle can target and disrupt the Golgi apparatus in tumor cells, which reduced PDT-mediated immunosuppression by blocking the production of immunosuppressive cytokines. This work provides an effective strategy of PDT in combination with the Golgi apparatus-targeted nanovesicle for enhanced cancer therapy.


Assuntos
Nanopartículas , Fotoquimioterapia , Porfirinas , Pró-Fármacos , Animais , Linhagem Celular Tumoral , Sulfatos de Condroitina , Citocinas , Complexo de Golgi , Fatores Imunológicos , Imunoterapia , Camundongos , Nanopartículas/uso terapêutico , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/farmacologia , Pró-Fármacos/farmacologia
4.
Nat Commun ; 12(1): 2174, 2021 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-33846342

RESUMO

Insufficient apoptosis of inflammatory macrophages and osteoclasts (OCs) in rheumatoid arthritis (RA) joints contributes toward the persistent progression of joint inflammation and destruction. Here, we deliver celastrol (CEL) to selectively induce apoptosis of OCs and macrophages in arthritic joints, with enzyme-responsive nanoparticles (termed PRNPs) composed of RGD modified nanoparticles (termed RNPs) covered with cleavable PEG chains. CEL-loaded PRNPs (CEL-PRNPs) dually target OCs and inflammatory macrophages derived from patients with RA via an RGD-αvß3 integrin interaction after PEG cleavage by matrix metalloprotease 9, leading to increased apoptosis of these cells. In an adjuvant-induced arthritis rat model, PRNPs have an arthritic joint-specific distribution and CEL-PRNPs efficiently reduce the number of OCs and inflammatory macrophages within these joints. Additionally, rats with advanced arthritis go into inflammatory remission with bone erosion repair and negligible side effects after CEL-PRNPs treatment. These findings indicate potential for targeting chemotherapy-induced apoptosis in the treatment of advanced inflammatory arthritis.


Assuntos
Apoptose , Artrite Reumatoide/patologia , Inflamação/patologia , Articulações/patologia , Macrófagos/patologia , Osteoclastos/patologia , Animais , Artrite Reumatoide/diagnóstico por imagem , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/patologia , Endocitose/efeitos dos fármacos , Feminino , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Articulações/diagnóstico por imagem , Lipopolissacarídeos/farmacologia , Camundongos Endogâmicos C57BL , Nanopartículas/química , Nanopartículas/ultraestrutura , Oligopeptídeos/química , Triterpenos Pentacíclicos , Ratos , Membrana Sinovial/diagnóstico por imagem , Membrana Sinovial/patologia , Distribuição Tecidual , Triterpenos , Microtomografia por Raio-X
5.
Biomaterials ; 258: 120296, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32781326

RESUMO

Palmitic acid-modified bovine serum albumin (PAB) was synthetized and found to own remarkable scavenger receptor-A (SR-A) targeting ability in vitro and in vivo, through which activated macrophages took up PAB nanoparticles (PAB NPs) 9.10 times more than bovine serum albumin nanoparticles (BSA NPs) and PAB NPs could delivery anti-inflammatory drugs celastrol (CLT) to inflamed tissues more effectively than BSA NPs. Compared with chondroitin sulfate modified BSA NPs targeting activated macrophages via CD44, PAB NPs show a more prominent targeting effect whether in vivo or in vitro. And PAB also demonstrated excellent biosafety compared to maleylated BSA, a known SR-A ligand that was lethal in our study. Furthermore, in adjuvant-induced arthritis rats, CLT-PAB NPs significantly improved disease pathology at a lower CLT dose with high safety, compared with CLT-BSA NPs. In addition, compared with the existing ligands with SR-A targeting due to strong electronegativity, the enhanced electronegativity and introduced PA are both important for the SR-A targeting effect of PAB. Therefore, PAB provides a novel direction for the treatment of rheumatoid arthritis and design of new ligands of SR-A.


Assuntos
Artrite Reumatoide , Nanopartículas , Animais , Artrite Reumatoide/tratamento farmacológico , Portadores de Fármacos/uso terapêutico , Macrófagos , Ácido Palmítico , Ratos , Receptores Depuradores , Soroalbumina Bovina/uso terapêutico
6.
Adv Sci (Weinh) ; 6(6): 1801868, 2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30937266

RESUMO

Chemotherapy turns tumor cells into "tumor vaccines" by immunogenic cell death (ICD). However, it remains a challenge to exploit chemotherapy-induced "tumor vaccines" for solid cancer immunotherapy due to the inefficient effector T cells activation and tumor microenvironment immunosuppression. Here, a matrix metalloprotease 2 responsive liposome (PEG-FA-Lip) composed of cleavable PEG chains covering the folate (FA)-modified liposome is developed to deliver ICD inducer doxorubicin. In breast cancer-bearing mice, PEG-FA-Lip targets both 4T1 breast cancer cells and M2-tumor associated macrophages (M2-TAMs) via FA-receptor mediated endocytosis, resulting in abundant "tumor vaccines" and efficient elimination of M2-TAMs. The combination of local cytosine-phosphate-guanine (CpG) therapy facilitates PEG-FA-Lip induced "tumor vaccines" to effectively arouse systematic effector T cells immune response through promoting dendritic cell maturation and immunostimulatory cytokines secretion. The simultaneous elimination of M2-TAMs ensures the activated effector T cells exert antitumor immunity within tumor via decreasing immunosuppressive cytokines secretion and tumor infiltration of Treg cells. After receiving the combined treatment, 30.1% of breast cancer-bearing mice (initial tumor volume > 100 mm3) achieves the goal of tumor eradication. Remarkably, this combination therapy greatly inhibits lung metastasis and controls the growth of already metastasized breast cancers (initial tumor volume > 100 mm3).

7.
Int J Pharm ; 540(1-2): 57-64, 2018 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-29408684

RESUMO

In this study, an inflammation-targeted delivery system based on a liposomal carrier was developed to deliver hydrophobic dexamethasone against arthritis. Using two FDA-approved excipients for intravenous injection, dexamethasone loaded liposome (Dex-Lip) was prepared by a thin-film hydration method. The biodistribution of 1,1'-dioctadecyl-3,3,3',3'-tetramethylindodicarbocyanine-loaded liposomes (DiD-Lips) were performed in rats with adjuvant-induced arthritis and demonstrated specific targeting efficacy in the disease site. DiD-Lips showed prolonged retention time in the inflammatory joint tissues compared with free DiD. Dex-Lips effectively suppressed the joint swelling in arthritis rats and significantly down-regulated serum pro-inflammatory cytokines including tumor necrosis factor-α and interleukin-1ß when compared to free dexamethasone. Furthermore, Dex-Lips had no significantly impact on the body weight, alleviated the hyperglycemia and improved haematological profiles of rheumatoid arthritis rats during the treatment process. Taken together, a safe liposomal delivery system was developed to achieve inflammation targeted therapy against arthritis.


Assuntos
Antirreumáticos/administração & dosagem , Artrite Experimental/tratamento farmacológico , Dexametasona/administração & dosagem , Articulações/efeitos dos fármacos , Lipídeos/química , Animais , Antirreumáticos/química , Antirreumáticos/farmacocinética , Artrite Experimental/sangue , Artrite Experimental/induzido quimicamente , Artrite Experimental/patologia , Dexametasona/química , Dexametasona/farmacocinética , Composição de Medicamentos , Adjuvante de Freund , Mediadores da Inflamação/sangue , Injeções Intravenosas , Interleucina-1beta/sangue , Articulações/metabolismo , Articulações/patologia , Lipossomos , Masculino , Ratos Sprague-Dawley , Tecnologia Farmacêutica/métodos , Distribuição Tecidual , Fator de Necrose Tumoral alfa/sangue
8.
J Mater Chem B ; 6(19): 3163-3180, 2018 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32254351

RESUMO

The safe and efficient targeted delivery of chemotherapeutic drugs has remained a challenge in metastatic breast cancer therapy. Herein, we report a rational drug delivery strategy of co-administering tumor-penetrating peptide-iRGD with self-assembled amphiphilic block copolymer nanoparticles (HA-PLA) to inhibit tumor growth and lung metastasis in 4T1 breast cancer xenograft bearing mice through increasing drug accumulation in the tumors, inducing receptor-mediated tumor cell targeting without causing severe side effects. In vitro, HA-PLA displayed sustained and pH-sensitive release behavior. The cellular uptake of HA-PLA on high CD44-expressing 4T1 cells was significantly higher than the endocytosis on low CD44-expressing L929 fibroblast cells. In vivo, HA-PLA significantly extended the blood circulation time of DOX, displayed no "accelerated blood clearance (ABC) phenomenon" after repeated injection and decreased the side effects of DOX. When combined with iRGD, the drug distribution and penetration of HA-PLA in tumors were remarkably increased, resulting in better antitumor efficacy and the longest whole survival. In particular, the co-administration of iRGD with HA-PLA greatly increased drug distribution in the lung, which contributed to the effective inhibition of the lung metastasis of breast cancer. Therefore, co-administering iRGD with HA-PLA is a promising approach for metastatic breast cancer therapy.

9.
ACS Appl Mater Interfaces ; 9(2): 1280-1292, 2017 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-28009503

RESUMO

A safe and efficient tumor-targeting strategy based on oligomeric hyaluronic acid (HA) modification and coadministration of tumor-penetrating peptide-iRGD was successfully developed. In this study, common liposomes (cLip) were modified by oligomeric HA to obtain HA-Lip. After injection into rats, HA-Lip showed good stealth in the bloodstream and lower liver distribution compared with cLip. Moreover, our HA-Lip could be internalized into B16F10 cells (CD44-overexpressing tumor cells) through HA-CD44 interaction. After systemic administration to B16F10 melanoma-bearing mice, HA-Lip showed an increased distribution in tumor due to the prolonged blood circulation time and the enhanced penetration and retention effect. When coadministered with iRGD, the tumor penetration of HA-Lip was significantly enhanced, which could promote HA-Lip internalization by tumors cells located in deep tumor regions through receptor-mediated endocytosis. Furthermore, doxorubicin (DOX)-loaded HA-Lip coadministering with iRGD showed much better antitumor effect compared to DOX-loaded cLip and DOX-loaded cLip in combination with iRGD. In systemic toxicity test, DOX-loaded HA-Lip could significantly decrease the cardiotoxicity and myelosuppression of DOX. Taken together, our results demonstrated that coadministration of oligomeric HA-modified liposomes with iRGD could be a promising treatment strategy for targeted therapy of melanoma.


Assuntos
Melanoma , Animais , Linhagem Celular Tumoral , Doxorrubicina , Ácido Hialurônico , Lipossomos , Camundongos , Peptídeos , Ratos
10.
Mol Pharm ; 14(1): 296-309, 2017 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-27936775

RESUMO

Chemotherapeutic agents trigger antitumor immune response through inducing immunogenic tumor cell death. However, severe toxicity to immune system and insufficient immunogenic cell death hinder chemotherapy from arousing efficient antitumor immunity in vivo. In this study, the cytotoxic drug, pirarubicin (THP), was entrapped into nanostructured lipid carriers (NLC); THP-NLC significantly reduced the toxicity of THP to immune system and improved immune status of breast cancer bearing mice. When THP-NLC was coinjected with iRGD (a tumor-penetrating peptide), drug accumulation in tumors was greatly elevated, which led to significant control of tumor growth and increase of immunogenic tumor cell death. Subsequently, the cytotoxic T lymphocytes (CD3+ and CD8+ cells) infiltration and cytokine (IFN-γ and INF-α) secretion in tumors were heavily increased. The efficient T-cell dependent control of tumors in the late stage and the lower side effects contributed to the longest whole survival of THP-NLC + iRGD treated mice. Therefore, the coadministration of THP-NLC with iRGD resulted in increased tumor cell direct-killing death and enhanced antitumor immune response. Our results illustrated that THP could serve as an immunogenic cell death inducer and the proposed drug delivery strategy might impact cancer immunotherapy by arousing increased immunogenic tumor cell death.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Doxorrubicina/análogos & derivados , Portadores de Fármacos/administração & dosagem , Imunidade/efeitos dos fármacos , Lipídeos/administração & dosagem , Nanoestruturas/administração & dosagem , Oligopeptídeos/administração & dosagem , Adjuvantes Farmacêuticos/administração & dosagem , Adjuvantes Farmacêuticos/química , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Doxorrubicina/administração & dosagem , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Feminino , Lipídeos/química , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Oligopeptídeos/química , Ratos , Ratos Sprague-Dawley , Linfócitos T Citotóxicos/efeitos dos fármacos
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