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Tugba Yildiz,1 Renpeng Gu,2 Stefan Zauscher,2 Tania Betancourt1,3 1Materials Science, Engineering, and Commercialization Program, Texas State University, San Marcos, TX, 2Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC, 3Department of Chemistry and Biochemistry, Texas State University, San Marcos, TX, USA Introduction: Despite significant progress in the field of oncology, cancer remains one of the leading causes of death. Chemotherapy is one of the most common treatment options for cancer patients but is well known to result in off-target toxicity. Theranostic nanomedicines that integrate diagnostic and therapeutic functions within an all-in-one platform can increase tumor selectivity for more effective chemotherapy and aid in diagnosis and monitoring of therapeutic responses. Material and methods: In this work, theranostic nanoparticles were synthesized with commonly used biocompatible and biodegradable polymers and used as cancer contrast and therapeutic agents for optical imaging and treatment of breast cancer. These core–shell nanoparticles were prepared by nanoprecipitation of blends of the biodegradable and biocompatible amphiphilic copolymers poly(lactic-co-glycolic acid)-b-poly-L-lysine and poly(lactic acid)-b-poly(ethylene glycol). Poly-L-lysine in the first copolymer was covalently decorated with near-infrared fluorescent Alexa Fluor 750 molecules. Results: The spherical nanoparticles had an average size of 60–80 nm. The chemotherapeutic drug doxorubicin was encapsulated in the core of nanoparticles at a loading of 3% (w:w) and controllably released over a period of 30 days. A 33-fold increase in near-infrared fluorescence, mediated by protease-mediated cleavage of the Alexa Fluor 750-labeled poly-L-lysine on the surface of the nanoparticles, was observed upon interaction with the model protease trypsin. The cytocompatibility of drug-free nanoparticles and growth inhibition of drug-loaded nanoparticles on MDA-MB-231 breast cancer cells were investigated with a luminescence cell-viability assay. Drug-free nanoparticles were found to cause minimal toxicity, even at high concentrations (0.2–2,000 µg/mL), while doxorubicin-loaded nanoparticles significantly reduced cell viability at drug concentrations >10 µM. Finally, the interaction of the nanoparticles with breast cancer cells was studied utilizing fluorescence microscopy, demonstrating the potential of the nanoparticles to act as near-infrared fluorescence optical imaging agents and drug-delivery carriers. Conclusion: Doxorubicin-loaded, enzymatically activatable nanoparticles of less than 100 nm were prepared successfully by nanoprecipitation of copolymer blends. These nanoparticles were found to be suitable as controlled drug delivery systems and contrast agents for imaging of cancer cells. Keywords: nanomedicine, theranostics, drug delivery, fluorescence imaging, enzymatic activation, nanoprecipitation, block copolymers, PLGA, PLA, PEG, poly-L-lysine, nanoparticles

Travis Cantu,1 Kyle Walsh,2 Varun P Pattani,3 Austin J Moy,3 James W Tunnell,3 Jennifer A Irvin,1,2 Tania Betancourt1,2 1Materials Science, Engineering, and Commercialization Program, Texas State University, San Marcos, TX, USA; 2Department of Chemistry and Biochemistry, Texas State University, San Marcos, TX, USA; 3Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, USA Abstract: Laser-mediated photothermal ablation of cancer cells aided by photothermal agents is a promising strategy for localized, externally controlled cancer treatment. We report the synthesis, characterization, and in vitro evaluation of conductive polymeric nanoparticles (CPNPs) of poly(diethyl-4,4'-{[2,5-bis(2,3-dihydrothieno[3,4-b][1,4]dioxin-5-yl)-1,4-phenylene]bis(oxy)}dibutanoate) (P1) and poly(3,4-ethylenedioxythiophene) (PEDOT) stabilized with 4-dodecylbenzenesulfonic acid and poly(4-styrenesulfonic acid-co-maleic acid) as photothermal ablation agents. The nanoparticles were prepared by oxidative-emulsion polymerization, yielding stable aqueous suspensions of spherical particles of

Abstract Background The conflict in eastern Democratic Republic of the Congo (DRC) is the deadliest since World War II. Over a decade of fighting amongst an array of armed groups has resulted in extensive human rights abuses, particularly the widespread use of sexual violence against women. Methods Using a mixed-methods approach, we surveyed a non-random sample of 255 women attending a referral hospital and two local non-governmental organizations to characterize their experiences of sexual and gender-based violence (SGBV). We then conducted focus groups of 48 women survivors of SGBV to elaborate on survey findings. Quantitative and qualitative data underwent thematic and statistical analysis respectively. Findings Of the women surveyed, 193 (75.7%) experienced rape. Twenty-nine percent of raped women were rejected by their families and 6% by their communities. Thirteen percent of women had a child from rape. Widowhood, husband abandonment, gang rape, and having a child from rape were significant risk factors for social rejection. Mixed methods findings show rape survivors were seen as "contaminated" with HIV, contributing to their isolation and over 95% could not access prophylactic care in time. Receiving support from their husbands after rape was protective against survivors' feelings of shame and social isolation. Interpretation Rape results not only in physical and psychological trauma, but can destroy family and community structures. Women face significant obstacles in seeking services after rape. Interventions offering long-term solutions for hyper-vulnerable women are vital, but lacking; reintegration programs on SGBV for women, men, and communities are also needed.

Background.: Suicide is a major global health concern. Bhutanese refugees resettled in the USA are disproportionately affected by suicide, yet little research has been conducted to identify factors contributing to this vulnerability. This study aims to investigate the issue of suicide of Bhutanese refugee communities via an in-depth qualitative, social-ecological approach. Methods.: Focus groups were conducted with 83 Bhutanese refugees (adults and children), to explore the perceived causes, and risk and protective factors for suicide, at individual, family, community, and societal levels. Audio recordings were translated and transcribed, and inductive thematic analysis conducted. Results.: Themes identified can be situated across all levels of the social-ecological model. Individual thoughts, feelings, and behaviors are only fully understood when considering past experiences, and stressors at other levels of an individual's social ecology. Shifting dynamics and conflict within the family are pervasive and challenging. Within the community, there is a high prevalence of suicide, yet major barriers to communicating with others about distress and suicidality. At the societal level, difficulties relating to acculturation, citizenship, employment and finances, language, and literacy are influential. Two themes cut across several levels of the ecosystem: loss; and isolation, exclusion, and loneliness. Conclusions.: This study extends on existing research and highlights the necessity for future intervention models of suicide to move beyond an individual focus, and consider factors at all levels of refugees' social-ecology. Simply focusing treatment at the individual level is not sufficient. Researchers and practitioners should strive for community-driven, culturally relevant, socio-ecological approaches for prevention and treatment. [ABSTRACT FROM AUTHOR]

Context: Prior qualitative work with internally displaced persons in war-affected northern Uganda showed significant mental health and psychosocial problems.Objective: To assess effect of locally feasible interventions on depression, anxiety, and conduct problem symptoms among adolescent survivors of war and displacement in northern Uganda.Design, Setting, and Participants: A randomized controlled trial from May 2005 through December 2005 of 314 adolescents (aged 14-17 years) in 2 camps for internally displaced persons in northern Uganda.Interventions: Locally developed screening tools assessed the effectiveness of interventions in reducing symptoms of depression and anxiety, ameliorating conduct problems, and improving function among those who met study criteria and were randomly allocated (105, psychotherapy-based intervention [group interpersonal psychotherapy]; 105, activity-based intervention [creative play]; 104, wait-control group [individuals wait listed to receive treatment at study end]). Intervention groups met weekly for 16 weeks. Participants and controls were reassessed at end of study.Main Outcome Measures: Primary measure was a decrease in score (denoting improvement) on a depression symptom scale. Secondary measures were improvements in scores on anxiety, conduct problem symptoms, and function scales. Depression, anxiety, and conduct problems were assessed using the Acholi Psychosocial Assessment Instrument with a minimum score of 32 as the lower limit for clinically significant symptoms (maximum scale score, 105).Results: Difference in change in adjusted mean score for depression symptoms between group interpersonal psychotherapy and control groups was 9.79 points (95% confidence interval [CI], 1.66-17.93). Girls receiving group interpersonal psychotherapy showed substantial and significant improvement in depression symptoms compared with controls (12.61 points; 95% CI, 2.09-23.14). Improvement among boys was not statistically significant (5.72 points; 95% CI, -1.86 to 13.30). Creative play showed no effect on depression severity (-2.51 points; 95% CI, -11.42 to 6.39). There were no statistically different improvements in anxiety in either intervention group. Neither intervention improved conduct problem or function scores.Conclusions: Both interventions were locally feasible. Group interpersonal psychotherapy was effective for depression symptoms among adolescent girls affected by war and displacement. Other interventions should be investigated to assist adolescent boys in this population who have symptoms of depression.Trial Registration: clinicaltrials.gov Identifier: NCT00280319. [ABSTRACT FROM AUTHOR]

Abstract Background Previous studies of Haitian immigrant and refugee youth have emphasized "externalizing" behaviors, such as substance use, high risk sexual behavior, and delinquency, with very little information available on "internalizing" symptoms, such as depression and anxiety. Analyzing stressors and "internalizing" symptoms offers a more balanced picture of the type of social and mental health services that may be needed for this population. The present study aims to: 1) estimate the prevalence of depression and post-traumatic stress disorder (PTSD) among Haitian immigrant students; and 2) examine factors associated with depression and PTSD to identify potential areas of intervention that may enhance psychosocial health outcomes among immigrant youth from Haiti in the U.S. Methods A stratified random sample of Haitian immigrant students enrolled in Boston public high schools was selected for participation; 84% agreed to be interviewed with a standardized questionnaire. Diagnosis of depression and PTSD was ascertained using the best estimate diagnosis method. Results The prevalence estimates of depression and PTSD were 14.0% and 11.6%; 7.9% suffered from comorbid PTSD and depression. Multivariate logistic regression demonstrated factors most strongly associated with depression (history of father's death, self-report of schoolwork not going well, not spending time with friends) and PTSD (concern for physical safety, having many arguments with parents, history of physical abuse, and lack of safety of neighborhood). Conclusions A significant level of depression and PTSD was observed. Stressors subsequent to immigration, such as living in an unsafe neighborhood and concern for physical safety, were associated with an increased risk of PTSD and should be considered when developing programs to assist this population. Reducing exposure to these stressors and enhancing access to social support and appropriate school-based and mental health services may improve educational attainment and psychosocial health outcomes among Haitian immigrant youth.

To improve their aqueous solubility characteristics, water-solubilizing groups were added to some antiproliferative, rigidin-inspired 7-deazahypoxanthine frameworks after molecular modeling seemed to indicate that structural modifications on the C7 and/or C8 phenyl groups would be beneficial. To this end, two sets of 7-deazahypoxanthines were synthesized by way of a multicomponent reaction approach. It was subsequently determined that their antiproliferative activity against HeLa cells was retained for those derivatives with a glycol ether at the 4'-position of the C8 aryl ring system, while also significantly improving their solubility behavior. The best of these compounds were the equipotent 6-[4-(2-ethoxyethoxy)benzoyl]-2-(pent-4-yn-1-yl)-5-phenyl-1,7-dihydro-4 H -pyrrolo[2,3- d ]pyrimidin-4-one 33 and 6-[4-(2-ethoxyethoxy)benzoyl]-5-(3-fluorophenyl)-2-(pent-4-yn-1-yl)-1,7-dihydro-4 H -pyrrolo[2,3- d ]pyrimidin-4-one 59 . Similarly to the parent 1 , the new derivatives were also potent inhibitors of tubulin assembly. In treated HeLa cells, live cell confocal microscopy demonstrated their impact on microtubulin dynamics and spindle morphology, which is the upstream trigger of mitotic delay and cell death.

Photoactivated chemotherapy (PACT) is a promising cancer treatment modality that kills cancer cells via photochemical uncaging of a cytotoxic drug. Most ruthenium-based photocages used for PACT are activated with blue or green light, which penetrates sub-optimally into tumor tissues. Here, we report amide functionalization as a tool to fine-tune the toxicity and excited states of a terpyridine-based ruthenium photocage. Due to conjugation of the amide group with the terpyridine π system in the excited state, the absorption of red light (630 nm) increased 8-fold, and the photosubstitution rate rose 5-fold. In vitro, red light activation triggered inhibition of tubulin polymerization, which led to apoptotic cell death both in normoxic (21 % O 2 ) and hypoxic (1 % O 2 ) cancer cells. In vivo, red light irradiation of tumor-bearing mice demonstrated significant tumor volume reduction (45 %) with improved biosafety, thereby demonstrating the clinical potential of this compound., (© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Introduction: In Colombia, research on health and conflict has focused on mental health, psychosocial care, displacement, morbidity, and mortality. Few scientific studies have assessed health system functioning during armed conflicts. In a new period characterized by the implementation of the peace agreement with the Revolutionary Armed Forces of Colombia (FARC) armed group, understanding the effects of armed conflict on the health system, the functions, and institutions shaped by the conflict is an opportunity to understand the pathways and scope of post-conflict health policy reforms. Therefore, this study was conducted to assess the effects of armed conflict on the health system, response, and mechanisms developed to protect medical missions during armed conflict in Colombia., Methods: This research was conducted using a qualitative approach with semi-structured interviews and focus group discussions. The qualitative guide collected information in four sections: (1) conflict and health system, effects and barriers in health service provision, (2) actions and coordination to cope with those barriers, (3) health policies and armed conflict, and (4) post-accord and current situation. Twenty-two people participated in the interviews, including eight policymakers at the national level and seven at the local level, including two NGOs and five members of international organizations. An academic project event in December 2019 and four focus groups were developed (World Cafe technique) to discuss with national and local stakeholders the effects of armed conflict on the health system and an analytical framework to analyze its consequences., Results: The conflict affected the health-seeking behavior of the population, limited access to healthcare provision, and affected health professionals, and was associated with inadequate medical supplies in conflict areas. The health system implemented mechanisms to protect the medical mission, regulate healthcare provision in conflict areas, and commit to healthcare provision (mental and physical health services) for the population displaced by conflict., Conclusion: The state's presence, trust, and legitimacy have significantly reduced in recent years. However, it is crucial to restore them by ensuring that state and health services are physically present in all territories, including remote and rural areas., (© 2023. The Author(s).)

Hydrogels are cross-linked three-dimensional polymer networks that have tissue-like properties. Dynamic covalent bonds (DCB) can be utilized as hydrogel cross-links to impart injectability, self-healing ability, and stimuli responsiveness to these materials. In our research, we utilized dynamic thiol-Michael bonds as cross-links in poly(ethylene glycol) (PEG)-based hydrogels. Because the equilibrium of the reversible, exothermic thiol-Michael reaction can be modulated by temperature, we investigated the possibility of using thermal and photothermal stimuli to modulate the gel-to-sol transition of these materials with the aim of developing an on-demand pulsatile cargo release system. For this purpose, we incorporated poly(3,4-ethylenedioxythiophene) (PEDOT) nanoparticles within the hydrogel to facilitate photothermal modulation using near-infrared light. PEDOT nanoparticles of 50 nm in diameter and with strong near-infrared absorption were prepared by oxidative emulsion polymerization. We then used Michael addition of thiol-ene pairs from 4-arm PEG-thiol (PEG-SH) and 4-arm PEG-benzylcyanoacetamide (PEG-BCA) to form dynamically cross-linked hydrogels. PEDOT nanoparticles were entrapped in situ to form Gel/PEDOT composites. Rheology and inverted tube test studies showed that the gel-to-sol transition occurred at 45-50 °C for 5 wt % gels and that this transition could be tailored by varying the wt % of the polymer precursors. The hydrogels were found to be capable of self-healing and being injected with a clinically relevant injection force. Bovine serum albumin-fluorescein isothiocyanate (BSA-FITC), a fluorescently labeled protein, was then loaded into the Gel/PEDOT as a therapeutic mimic. Increased release of BSA-FITC upon direct thermal stimulation and photothermal stimulation with an 808 nm laser was observed. Pulsatile release of BSA-FITC over seven cycles was demonstrated. MTS and live-dead assays demonstrated that Gel/PEDOT was cytocompatible in MDA-MB-231 breast cancer and 3T3 fibroblast cell lines. Further studies demonstrated that the encapsulation and laser-triggered release of the chemotherapeutic agent doxorubicin (DOX) could also be achieved. Altogether, this work advances our understanding of the temperature-dependent behavior of a dynamic covalent hydrogel, Gel/PEDOT , and leverages that understanding for application as a photothermally responsive biomaterial for controlled release.

Two case studies of parenting programs, aiming to improve parenting practices and child development outcomes, and implemented by Save the Children/Ministry of Health/Khesar Gyalpo University in Bhutan and Boston College/University of Rwanda/FXB in Rwanda, respectively called Prescription to Play and Sugira Muryango, were conducted by an independent research and learning group. Implementation research focused on the workforce, a crucial but little-studied element determining the success of programs going to scale. Mixed methods were used to examine their training, workload, challenges, and quality of delivery. Health assistants in Bhutan and volunteers in Rwanda were trained for 10-11 days using demonstrations, role plays, and manuals outlining activities to deliver to groups of parents (Bhutan) or during home visits (Rwanda). Workers' own assessments of their delivery quality, their confidence, and their motivations revealed that duty, confidence, and community respect were strong motivators. According to independent observations, the quality of their delivery was generally good, with an overall mean rating on 10 items of 2.36 (Bhutan) and 2.44 (Rwanda) out of 3. The facilitators of scaling for Bhutan included institutionalizing training and a knowledgeable workforce; the barrier was an overworked workforce. The facilitators of scaling for Rwanda included strong follow-up supervision; the barriers included high attrition among a volunteer workforce.

Nanomedicine is a novel field of study that involves the use of nanomaterials to address challenges and issues that are associated with conventional therapeutics for cancer treatment including, but not limited to, low bioavailability, low water-solubility, narrow therapeutic window, nonspecific distribution, and multiple side effects of the drugs. Multiple strategies have been exploited to reduce the nonspecific distribution, and thus the side effect of the active pharmaceutical ingredients (API), including active and passive targeting strategies and externally controllable release of the therapeutic cargo. Site-specific release of the drug prevents it from impacting healthy cells, thereby significantly reducing side effects. API release triggers can be either externally applied, as in ultrasound-mediated activation, or induced by the tumor. To rationally design such nanomedicines, a thorough understanding of the differences between the tumor microenvironment versus that of healthy tissues must be paired with extensive knowledge of stimuli-responsive biomaterials. Herein, we describe the characteristics that differentiate tumor tissues from normal tissues. Then, we introduce smart materials that are commonly used for the development of smart nanomedicines to be triggered by stimuli such as changes in pH, temperature, and enzymatic activity. The most recent advances and their impact on the field of cancer therapy are further discussed., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Recent focus on cancer immunotherapies has led to significant interest in the development of therapeutic strategies that can lead to immunogenic cell death (ICD), which can cause activation of an immune response against tumor cells and improve immunotherapy outcomes by enhancing the immunogenicity of the tumor microenvironment. In this work, a nanomedicine-mediated combination therapy is used to deliver the ICD inducers doxorubicin (Dox), a chemotherapeutic agent, and indocyanine green (ICG), a photothermal agent. These agents are loaded into nanoparticles (NPs) of bovine serum albumin (BSA) that are prepared through a desolvation process. The formulation of BSA NPs is optimized to achieve NPs of 102.6  nm in size and loadings of 8.55 % and 5.69 % (w/w) for ICG and Dox, respectively. The controlled release of these agents from the BSA NPs is confirmed. Upon laser irradiation for 2.5 min, NPs at a dose of 62.5 μg mL -1 are able to increase the temperature of the cells by 7 °C and thereby inhibit the growth of B16F10 melanoma cells in vitro. Surface presentation of heat shock proteins and calreticulin from the cells after treatment confirmed the ability of the Dox/ICG loaded BSA NPs to induce ICD in the melanoma cells., (© 2021 Wiley-VCH GmbH.)

Indolizines and pyrazolo[1,5-a]pyridines were prepared via [3 + 2]-cycloaddition of pyridinium ylides to 1-chloro-2-nitrostyrenes. The synthesized molecules were evaluated for antiproliferative activities against a BE(2)-C neuroblastoma cell line with several compounds decreasing the viability of cancer cells. Indolizine 9db showed higher potency than that of all-trans-retinoic acid, an approved cancer drug. Mechanistically, it was found to inhibit tubulin polymerization and it is thus proposed that the discovered chemistry can be exploited for the development of novel microtubule-targeting anticancer agents.

Recent advances in immunotherapy have highlighted a need for therapeutics that initiate immunogenic cell death in tumors to stimulate the body's immune response to cancer. This study examines whether laser-generated bubbles surrounding nanoparticles ("nanobubbles") induce an immunogenic response for cancer treatment. A single nanosecond laser pulse at 1064 nm generates micron-sized bubbles surrounding gold nanorods in the cytoplasm of breast cancer cells. Cell death occurred in cells treated with nanorods and irradiated, but not in cells with irradiation treatment alone. Cells treated with nanorods and irradiation had increased damage-associated molecular patterns (DAMPs), including increased expression of chaperone proteins human high mobility group box 1 (HMGB1), adenosine triphosphate (ATP), and heat shock protein 70 (HSP70). This enhanced expression of DAMPs led to the activation of dendritic cells. Overall, this treatment approach is a rapid and highly specific method to eradicate tumor cells with simultaneous immunogenic cell death signaling, showing potential as a combination strategy for immunotherapy.

Background: Past trauma and exposure to violence have been related to poor emotion regulation and household violence, which can have persistent mental health effects across generations. The Family Strengthening Intervention for Early Childhood Development (FSI-ECD/called Sugira Muryango in Rwanda) is an evidence-based behavioral home-visiting intervention to promote caregiver mental health, positive parenting practices, and early childhood development among families facing adversity. In Sierra Leone and other lower- and middle-income countries, mobile health (mHealth) technology has the potential to improve health care delivery and health outcomes., Objective: This study aims to (1) apply a user-centered design to develop and test mHealth tools to improve supervision and fidelity monitoring of community health workers (CHWs) delivering the FSI-ECD and (2) conduct a pilot randomized controlled trial of the FSI-ECD to assess feasibility, acceptability, and preliminary effects on caregiver mental health, emotion regulation, caregiving behaviors, and family violence in high-risk families with children aged 6-36 months in comparison with control families receiving standard care., Methods: We will recruit and enroll CHWs, supervisors, and families with a child aged 6-36 months from community health clinics in Sierra Leone. CHWs and supervisors will participate in 1 problem analysis focus group and 2 user interface/user experience cycles to provide feedback on mHealth tool prototypes. Families will be randomized to mHealth-supported FSI-ECD or standard maternal and child health services. We will collect quantitative data on caregiver mental health, emotion regulation, caregiving behaviors, and family functioning at baseline, postintervention, and 3-month follow up. We will use a mixed methods approach to explore feasibility and acceptability of mHealth tools and the FSI-ECD. Mixed effects linear modeling will assess FSI-ECD effects on caregiver outcomes. Cost-effectiveness analysis will estimate costs across FSI-ECD versus standard care., Results: Funding for this study was received from the National Institutes of Mental Health on August 17, 2020. Institutional Review Board approval was received on September 4, 2020. Data collection is projected to begin on December 15, 2020., Conclusions: This study will provide important data on the feasibility, acceptability, and preliminary efficacy of mHealth-supported delivery of an evidence-based family home-visiting intervention in a postconflict LMIC., Trial Registration: ClinicalTrials.gov NCT04481399; https://clinicaltrials.gov/ct2/show/NCT04481399., International Registered Report Identifier (irrid): PRR1-10.2196/25443., (©Alethea Desrosiers, Carolyn Schafer, Rebecca Esliker, Musu Jambai, Theresa Betancourt. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 02.02.2021.)

Worldwide, over 70.8 million people are forcibly displaced from their homes as a result of persecution, conflict, violence, or human rights violation. In humanitarian crises, protection and the provision of basic needs are often prioritized. Research may be seen as opportunistic. However, without documenting and researching humanitarian responses, knowledge is not shared and does not accumulate, limiting the application of evidence-based interventions where they are most needed. Research in humanitarian crises is complex, both ethically and methodologically. Community-engaged research, and specifically community-based participatory research (CBPR), can address some of the challenges of research in these settings. Using case studies of research we have conducted with communities affected by humanitarian crises, we highlight challenges and opportunities of the application of the ten core principles of CBPR in humanitarian settings. Despite some challenges and barriers, CBPR is a highly effective approach to use when engaging these populations in research. We argue that the application of CBPR in these settings has the potential to recalibrate the scales of equity and power among vulnerable populations., (© 2020 Society for Community Research and Action.)

The use of nanomedicines to induce immunogenic cell death is a new strategy that aims to increase tumor immunogenicity and thereby prime tumors for further immunotherapies. In this study, we developed a nanoparticle formulation for combinatory chemotherapy and photothermal therapy based only on materials previously used in FDA-approved products and investigated the effect of the combinatory therapy on the growth inhibition and induction of immunogenic cell death in human MDA-MB-231 breast cancer cells. The formulation consists of ~108-nm nanoparticles made of poly(lactic acid)-b-methoxy poly(ethylene glycol) which carry doxorubicin for chemotherapy and indocyanine green for photothermal therapy. A 0.3 mg/mL suspension of NPs increased the medium temperature up to 10 °C upon irradiation with an 808-nm diode laser. In vitro studies showed that combination of laser assisted indocyanine green-mediated photothermal therapy and doxorubicin-mediated chemotherapy effectively eradicated cancer cells and resulted in the highest level of damage-associated molecular pattern presentation (calreticulin, high mobility group box 1, and adenosine triphosphate) compared to the individual treatments alone. These results demonstrate that our nanoparticle-mediated combinatory approach led to the most intense immunogenic cell death when compared to individual chemotherapy or photothermal therapy, making it a potent option for future in vivo studies in combination with cancer immunotherapies., (Copyright © 2020 Elsevier B.V. All rights reserved.)