Baharak Bahmani

Bio: Baharak Bahmani is an academic researcher from Brigham and Women's Hospital. The author has contributed to research in topics: Nanocapsules & Indocyanine green. The author has an hindex of 12, co-authored 28 publications receiving 493 citations. Previous affiliations of Baharak Bahmani include Amirkabir University of Technology & University of California, Riverside.

Intratumoral immunotherapy using platelet-cloaked nanoparticles enhances antitumor immunity in solid tumors

Abstract: Intratumoral immunotherapy is an emerging modality for the treatment of solid tumors. Toll-like receptor (TLR) agonists have shown promise for eliciting immune responses, but systemic administration often results in the development of adverse side effects. Herein, we investigate whether localized delivery of the TLR agonist, resiquimod (R848), via platelet membrane-coated nanoparticles (PNP-R848) elicits antitumor responses. The membrane coating provides a means of enhancing interactions with the tumor microenvironment, thereby maximizing the activity of R848. Intratumoral administration of PNP-R848 strongly enhances local immune activation and leads to complete tumor regression in a colorectal tumor model, while providing protection against repeated tumor re-challenges. Moreover, treatment of an aggressive breast cancer model with intratumoral PNP-R848 delays tumor growth and inhibits lung metastasis. Our findings highlight the promise of locally delivering immunostimulatory payloads using biomimetic nanocarriers, which possess advantages such as enhanced biocompatibility and natural targeting affinities.

Erythrocyte-derived photo-theranostic agents: hybrid nano-vesicles containing indocyanine green for near infrared imaging and therapeutic applications

Abstract: Development of theranostic nano-constructs may enable diagnosis and treatment of diseases at high spatial resolution Some key requirements for clinical translation of such constructs are that they must be non-toxic, non-immunogenic, biodegradable, with extended circulating lifetime Cell-based structures, particularly those derived from erythrocytes, are promising candidate carrier systems to satisfy these requirements One particular type of theranostic materials utilize light-sensitive agents that once photo-activated can provide diagnostic imaging capability, and elicit therapeutic effects Here we demonstrate the first successful engineering of hybrid nano-scale constructs derived from membranes of hemoglobin-depleted erythrocytes that encapsulate the near infrared chromophore, indocyanine green We show the utility of the constructs as photo-theranostic agents in fluorescence imaging and photothermal destruction of human cells These erythrocyte-mimicking nano-structures can be derived autologously, and may have broad applications in personal nanomedicine ranging from imaging and photo-destruction of cancerous tissues to vascular abnormalities, and longitudinal evaluations of therapeutic interventions

Coatings of polyethylene glycol for suppressing adhesion between solid microspheres and flat surfaces.

Abstract: This article describes the development and the examination of surface coatings that suppress the adhesion between glass surfaces and polymer microspheres. Superparamagnetic doping allowed for exerting magnetic forces on the microbeads. The carboxyl functionalization of the polymer provided the means for coating the beads with polyethylene glycol (PEG) with different molecular weight. Under gravitational force, the microbeads settled on glass surfaces with similar polymer coatings. We examined the efficacy of removing the beads from the glass surfaces by applying a pulling force of ∼1.2 pN. The percent beads remaining on the surface after applying the pulling force for approximately 5 s served as an indication of the adhesion propensity. Coating of PEG with molecular weight ranging between 3 and 10 kDa was essential for suppressing the adhesion. For the particular substrates, surface chemistry and aqueous media we used, coatings of 5 kDa manifested optimal suppression of adhesion: that is, only 3% of the m...

Targeted delivery of immune therapeutics to lymph nodes prolongs cardiac allograft survival

Abstract: The targeted delivery of therapeutic drugs to lymph nodes (LNs) provides an unprecedented opportunity to improve the outcomes of transplantation and immune-mediated diseases. The high endothelial venule is a specialized segment of LN vasculature that uniquely expresses peripheral node addressin (PNAd) molecules. PNAd is recognized by MECA79 mAb. We previously generated a MECA79 mAb-coated microparticle (MP) that carries tacrolimus. Although this MP trafficked to LNs, it demonstrated limited therapeutic efficacy in our transplant model. Here, we have synthesized a nanoparticle (NP) as a carrier of anti-CD3, and optimized the conjugation strategy to coat the NP surface with MECA79 mAb (MECA79-anti-CD3-NP) to enhance LN accumulation. As compared with nonconjugated NPs, a significantly higher quantity of MECA79-NPs accumulated in the draining lymph node (DLN). Many MECA79-NPs underwent internalization by T cells and dendritic cells within the LNs. Short-term treatment of murine cardiac allograft recipients with MECA79-anti-CD3-NP resulted in significantly prolonged allograft survival in comparison with the control groups. Prolonged graft survival following treatment with MECA79-anti-CD3-NP was characterized by a significant increase in intragraft and DLN Treg populations. Treg depletion abrogated the prolongation of heart allograft survival. We believe this targeted approach of drug delivery could redefine the methods of administering immune therapeutics in transplantation.

Functionalized polymeric nanoparticles loaded with indocyanine green as theranostic materials for targeted molecular near infrared fluorescence imaging and photothermal destruction of ovarian cancer cells.

Abstract: Background and Objectives Ovarian cancer remains the deadliest malignancy of the female reproductive system The ability to identify and destroy all ovarian tumor nodules may have a termendous impact on preventing tumor recurrence, and patient survival The objective of this study is to investigate the effectiveness of a nano-structured system for combined near infrared (NIR) fluorescence imaging of human epidermal growth factor receptor-2 (HER2) over-expression, as a biomarker of ovarian cancer cells, and photothermal destruction of these cells in vitro Materials and Methods The nano-structured system consists of the near infrared dye, indocyanine green (ICG), encapsulated within poly(allylamine) hydrochloride chains cross-linked ionically with sodium phosphate The surface of the construct is functionalized by covalently attached polyethylene glycol, and monoclonal antibodies against HER2 using reducitve amination methods We use dynamic light scattering, and absorption and fluorescence spectroscopy for phyiscal characterization of the constructs Flow cytometry and fluorescence microscopy are used to investigate molecular targeting and imaging capabilities of the constructs against SKOV3 and OVCAR3 ovarian cancer cell lines, which have relatively high and low expression levels of the HER2 receptor, respectively Continuous NIR laser irradiation at 808 nm is used to investigating the utility of the constructs in mediating photothermal destruction of SKOV3 cells Results Flow cytometry results indicate that the functionalized nano-constructs are more effective in targeting the HER2 receptor than non-encapsulated ICG and non-functionlaized constructs (P < 0005) Fluorescence microscopic images show the capaiblity of the functionalized constructs in NIR imaging of HER2 overexpression The functionalized nano-constructs are also capable of inducing a significantly greater increase in photothermal destruction of SKOV3 cells than free ICG and non-functionalized constructs (P < 0005) Conclusion We have demonstrated the efficacy of polymeric nano-structured constructs loaded with ICG, and functionalized with the monoclonal antibodies, as thernaostic materials for targted molecular NIR imaging of the HER2 receptor overexpression on ovarian cancer cells, and photothermal destruction of these cells These nanoparticles may prove useful towards intraoperative detection, imaging, and phototherapy of small ovarian cancer nodules Lasers Surg Med 46:582–592, 2014 © 2014 Wiley Periodicals, Inc

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

Cancer nanomedicine for combination cancer immunotherapy

Abstract: Cancer immunotherapy is revolutionizing oncology. However, dose-limiting toxicities and low patient response rates remain major challenges in the clinic. Cancer nanomedicine in combination with immunotherapies offers the possibility to amplify antitumour immune responses and to sensitize tumours to immunotherapies in a safe and effective manner. In this Review, we discuss opportunities for combination immunotherapy based on nanoparticle platforms designed for chemotherapy, photothermal therapy, photodynamic therapy, radiotherapy and gene therapy. We highlight how nanoparticles can be used to reprogramme the immunosuppressive tumour microenvironment and to trigger systemic antitumour immunity, synergizing with immunotherapies against advanced cancer. Finally, we discuss strategies to improve tumour and immune cell targeting while minimizing toxicity and immune-related adverse events, and we explore the potential of theranostic nanoparticles for combination immunotherapy. Cancer nanomedicine in combination with immunotherapies offers the possibility to amplify antitumour immune responses and to sensitize tumours to immunotherapies. In this Review, the authors discuss combination immunotherapy based on nanoparticle platforms designed for chemotherapy, photothermal therapy, photodynamic therapy, radiotherapy and gene therapy.

Cell or Cell Membrane-Based Drug Delivery Systems

Abstract: Natural cells have been explored as drug carriers for a long period. They have received growing interest as a promising drug delivery system (DDS) until recently along with the development of biology and medical science. The synthetic materials, either organic or inorganic, are found to be with more or less immunogenicity and/or toxicity. The cells and extracellular vesicles (EVs), are endogenous and thought to be much safer and friendlier. Furthermore, in view of their host attributes, they may achieve different biological effects and/or targeting specificity, which can meet the needs of personalized medicine as the next generation of DDS. In this review, we summarized the recent progress in cell or cell membrane-based DDS and their fabrication processes, unique properties and applications, including the whole cells, EVs and cell membrane coated nanoparticles. We expect the continuing development of this cell or cell membrane-based DDS will promote their clinic applications.