L'Héparane Sulfate (HS), un polysaccharide linéaire, module les activités biologiques de nombreuses protéines. Afin d'élucider les interactions entre l'HS et les protéines, la synthèse chimique d'HS est un outil précieux, mais elle peut être difficile. Notre équipe a montré que des mélanges combinatoires obtenus par auto-assemblage de différentes combinaisons de dérivés disaccharidiques (lactose et lactose persulfaté) sur surfaces planes d'or peuvent reconnaître spécifiquement certaines protéines se liant à l'HS, telles que les isoformes de la chimiokine CXCL12 ou IFNγ. Avec ces dérivés, nous avons réalisé un auto-assemblage sur des nanoparticules d'or. Mais à cause de la toxicité des nanoparticules d'or, nous avons aussi adapté cette méthode à des nanoparticules lipidiques. En utilisant les conditions qui ont déjà été améliorées pendant la synthèse des dérivés lactose et lactose persulfaté, nous avons préparé deux autres dérivés disaccharidiques plus proches de la structure réelle d'HS. Ces nouveaux dérivés sont utilisés pour réaliser des nanoparticules d'or et nanoparticules lipidiques afin de comparer les propriétés avec les lactose et lactose persulfaté. Les tests d'affinité avec différentes protéines sont en cours de réalisation. / Héparan Sulfate (HS) is a linear polysaccharide that modulates the biological activities of numerous proteins. In order to elucidate the interaction between HS and proteins, the synthesis of HS is an invaluable tool, but the synthesis is sometimes difficult. Our group has demonstrated that the combinatorial mixtures obtained by self-assembly of different combinations of disaccharide derivatives (lactose and persulfated lactose) on gold plan surfaces could recognize specifically some HS binding proteins, such as the isoforms of the chemokine CXCL12 or IFNγ. Because of the toxicity of gold nanoparticles, we have also adapted this method to lipid nanoparticles. Using the conditions that have already improved during the synthesis of lactose and persulfated lactose derivatives, we have synthesized two other disaccharide derivatives, which were closer to the real structure of HS. These new derivatives were used to prepare the gold and lipid nanoparticles at the aim of comparing the properties with lactose and persulfated lactose. The tests of affinities with different proteins are in progress.

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Introdução: O câncer de ovário é frequentemente diagnosticado em estágios avançados e é pouco responsivo aos tratamentos empregados atualmente. O tratamento de primeira linha consiste em esquemas incluindo cirurgia citorredutora seguido de quimioterapia adjuvante por derivados de platina e taxano. Os esquemas de segunda linha são baseados em gemcitabina e doxorrubicina lipossomal. Em seguida, a doença tende a progredir rapidamente e a quimioterapia não é indicada pela ausência de resposta e pela alta toxicidade desses medicamentos. Anteriormente, mostramos que nanopartículas lipídicas semelhantes à composição química da LDL, porém sem proteína, e associadas à agentes antineoplásicos são captadas por células neoplásicas. Objetivos: Testamos a hipótese se o paclitaxel associado à nanopartícula poderia beneficiar com segurança pacientes com câncer de ovário avançado e refratário ao tratamento, e portanto, não mais elegíveis para quimioterapia convencional. Métodos: Quatorze mulheres com câncer de ovário avançado de 61 ± 10 anos, com estadiamento clínico IV e TqNqM1 (FIGO e TNM Scale, respectivamente) que não eram responsivas à quimioterapia em terceira linha foram incluídas no estudo. O tratamento consistiu com o paclitaxel associado à nanopartícula na dose 175 mg/m2 de superfície corporal, a cada 3 semanas. As pacientes foram submetidas a exames clínicos antes de cada ciclo de quimioterapia. Determinações bioquímicas séricas e exames de imagem foram realizados para acompanhamento de novas lesões ou progressão da doença. Resultados: Foi realizado o total de 74 ciclos, e não foram observadas toxicidades laboratoriais e clínicas. Em quatro pacientes a doença permaneceu estável. Conclusões: A notável ausência de toxicidade, não registrada na literatura até hoje nos vários sistemas de veiculação descritos abre uma nova perspectiva de tratamento da doença. Evita-se o desconforto e os riscos da quimioterapia convencional, podem ser incluídos pacientes muito idosos ou com outras fragilidades que contraindiquem a quimioterapia e não há limite para a continuação do tratamento. / Introduction: Ovarian cancer is often diagnosed at advanced stages and is poorly responsive to standard treatment. First-line treatment consists in schemes including citorreductive surgery followed by adjuvant chemotherapy schemes with platinum and taxane derivatives. Second-line regimens are based in gemcitabine and liposomal doxorubicin. Thereafter, the disease progresses rapidly and chemotherapy is no longer indicated for lack of response rate together with high toxicity of antineoplastic agents. Previously, we showed that non-protein lipid nanoparticles resembling chemical structure of LDL, however without protein and associated with antineoplastic agents are uptaken by neoplastic cells. Aims: We tested the hypothesis whether paclitaxel associated to the nanoparticle could safely benefit patients with advanced ovarian cancer refractory to previous treatment, thus not eligible for further conventional chemotherapy. Methodology: Fourteen women with advanced ovarian cancer aged 61 ± 10 years were included, with clinical stage IV and TqNqM1 (FIGO and TNM Scale, respectively) that were unresponsive for third line chemotherapy treatments. Treatment consisted with paclitaxel associated to the nanoparticle at 175 mg/m2 body surface dose, every 3 weeks. Patients were submitted to clinical examinations before each chemotherapy cycle. Serum biochemistry determinations and imaging exams were performed to monitoring new lesions or disease progression. Results: Total of 74 cycles of chemotherapy was performed, clinical and laboratorial toxicities were not observed. Four patients stayed with stable disease. Conclusions: The notable absence of toxicity, not recorded in the oncology literature to date described in various drug delivery systems, opens a new perspective on the treatment of cancer. Avoiding the discomfort and risks of conventional chemotherapy, can be included very aged patients or with other weaknesses, that chemotherapy is contraindicated, and there is no limit for continued treatment.

Introdução: O câncer de ovário é frequentemente diagnosticado em estágios avançados e é pouco responsivo aos tratamentos empregados atualmente. O tratamento de primeira linha consiste em esquemas incluindo cirurgia citorredutora seguido de quimioterapia adjuvante por derivados de platina e taxano. Os esquemas de segunda linha são baseados em gemcitabina e doxorrubicina lipossomal. Em seguida, a doença tende a progredir rapidamente e a quimioterapia não é indicada pela ausência de resposta e pela alta toxicidade desses medicamentos. Anteriormente, mostramos que nanopartículas lipídicas semelhantes à composição química da LDL, porém sem proteína, e associadas à agentes antineoplásicos são captadas por células neoplásicas. Objetivos: Testamos a hipótese se o paclitaxel associado à nanopartícula poderia beneficiar com segurança pacientes com câncer de ovário avançado e refratário ao tratamento, e portanto, não mais elegíveis para quimioterapia convencional. Métodos: Quatorze mulheres com câncer de ovário avançado de 61 ± 10 anos, com estadiamento clínico IV e TqNqM1 (FIGO e TNM Scale, respectivamente) que não eram responsivas à quimioterapia em terceira linha foram incluídas no estudo. O tratamento consistiu com o paclitaxel associado à nanopartícula na dose 175 mg/m2 de superfície corporal, a cada 3 semanas. As pacientes foram submetidas a exames clínicos antes de cada ciclo de quimioterapia. Determinações bioquímicas séricas e exames de imagem foram realizados para acompanhamento de novas lesões ou progressão da doença. Resultados: Foi realizado o total de 74 ciclos, e não foram observadas toxicidades laboratoriais e clínicas. Em quatro pacientes a doença permaneceu estável. Conclusões: A notável ausência de toxicidade, não registrada na literatura até hoje nos vários sistemas de veiculação descritos abre uma nova perspectiva de tratamento da doença. Evita-se o desconforto e os riscos da quimioterapia convencional, podem ser incluídos pacientes muito idosos ou com outras fragilidades que contraindiquem a quimioterapia e não há limite para a continuação do tratamento. / Introduction: Ovarian cancer is often diagnosed at advanced stages and is poorly responsive to standard treatment. First-line treatment consists in schemes including citorreductive surgery followed by adjuvant chemotherapy schemes with platinum and taxane derivatives. Second-line regimens are based in gemcitabine and liposomal doxorubicin. Thereafter, the disease progresses rapidly and chemotherapy is no longer indicated for lack of response rate together with high toxicity of antineoplastic agents. Previously, we showed that non-protein lipid nanoparticles resembling chemical structure of LDL, however without protein and associated with antineoplastic agents are uptaken by neoplastic cells. Aims: We tested the hypothesis whether paclitaxel associated to the nanoparticle could safely benefit patients with advanced ovarian cancer refractory to previous treatment, thus not eligible for further conventional chemotherapy. Methodology: Fourteen women with advanced ovarian cancer aged 61 ± 10 years were included, with clinical stage IV and TqNqM1 (FIGO and TNM Scale, respectively) that were unresponsive for third line chemotherapy treatments. Treatment consisted with paclitaxel associated to the nanoparticle at 175 mg/m2 body surface dose, every 3 weeks. Patients were submitted to clinical examinations before each chemotherapy cycle. Serum biochemistry determinations and imaging exams were performed to monitoring new lesions or disease progression. Results: Total of 74 cycles of chemotherapy was performed, clinical and laboratorial toxicities were not observed. Four patients stayed with stable disease. Conclusions: The notable absence of toxicity, not recorded in the oncology literature to date described in various drug delivery systems, opens a new perspective on the treatment of cancer. Avoiding the discomfort and risks of conventional chemotherapy, can be included very aged patients or with other weaknesses, that chemotherapy is contraindicated, and there is no limit for continued treatment.

Orientador: Maria Helena Andrade Santana / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Química / Made available in DSpace on 2018-08-18T18:45:10Z (GMT). No. of bitstreams: 1 Rossan_MarcosRoberto_M.pdf: 4251170 bytes, checksum: f64611ade06535fb615dbd4f23afd20f (MD5) Previous issue date: 2011 / Resumo: Neste trabalho, estudou-se o desenvolvimento tecnológico de micro/ nanopartículas lipídicas sólidas para aplicação cosmética capilar. As micropartículas foram produzidas por spray cooling, onde incorporou-se na matriz lipídica, composta por ceras naturais de origem vegetal (cera de carnaúba), mineral (microparafina) e sintética (cera de silicone), um ativo doador de brilho capilar, de nome comercial Activeshine Amazon, composto por uma mistura de triglicerídeos de murumuru e babaçú. As micropartículas foram obtidas a partir de misturas contendo 30% das ceras, porém a incorporação total do ativo na matriz lipídica ocorreu a partir de 70% de cera. A produção das micropartículas foi estudada através de um planejamento estatístico de experimentos e analise de superfície de resposta, onde determinou-se a influência da pressão do ar de atomização e concentração da cera, sobre o diâmetro médio. Os resultados mostraram que a pressão do ar de atomização foi a principal variável de significância estatística para os três tipos de ceras. Foram obtidas micropartículas esféricas, com diâmetro entre 30 - 320 ?m. As nanopartículas foram obtidas a partir da mistura lipídica composta por 50% de Activeshine Amazon e 50% de cera de carnaúba, além de sorbitol, óleo de mamona PEG-40 e quaternários de amônio (CTAC, BTAC e SDBAC), via nano-emulsificação de baixa energia, através do processo de inversão de fase por temperatura. Foram obtidas partículas com 0,08 a 0,35 de polidispersidade, 45 - 190 nm de diâmetro médio, e -20 A +70 mV de potencial zeta. Nestes estudos, verificou-se a influência destes componentes da formulação sobre o ponto de inversão de fase, comprovado por medidas de condutividade elétrica. Estes resultados mostram que os processos de spray cooling e nano-emulsificação utilizando ceras e triglicerídios produzem micro e nanopartículas que atendem aos requisitos de diâmetro médio, polidispersidade e potencial zeta para aplicação capilar. Essas partículas são também potencialmente úteis para a encapsulação de bioativos e desenvolvimento de formulações mais eficazes comparadas às que utilizam os compostos livres / Abstract: This work studied the technological development of solid lipid micro and nanopaparticles for cosmetic hair application. The microparticles were produced through spray cooling process, in which an active donator of hair brightness, commercially named Activeshine Amanzon was incorporated. The solid lipid matrix was composed by waxes from vegetal (carnauba), mineral (microparaffin) and synthetic (silicon) origin. The Activeshine Amazon is a mixture of triglycerides from murumuru butter and babassu oil. The microparticles were obtained from admixtures containing 30% of the waxes, but the total incorporation of the active in the lipid matrix occurred from 70% only. The production of microparticles was studied through a statistical experimental planning and surface response analysis from which it was determined the influence of the inlet atomization air pressure and wax concentration on the mean diameter of the particles. The results shown the air pressure was the statistically main significant variable for the three studied waxes. The mean diameter of the obtained spherical microparticles was in the range of 30 to 320 ?m. The nanoparticles were obtained through low-energy nano-emulsification process, known as temperature phase inversion. They were composed by a mixture of 50% Activeshine Amazon and 50% of carnauba wax, in which was also added sorbitol, castor oil PEG-40 and the ammonium quaternaries CTAC, BTAC and SDBAC. They presented 0.08 to 0.35 polydispersity, 45 to 190 nm mean diameter and -20 to + 70 mV zeta potential. The visual influence of the components of the formulation on the inversion phase temperature was comproved by electrical conductivity measurements. From these results we conclude that the spray cooling and nano-emulsification processes which use triglycerides as raw materials produce nano and microparticles which to meet the mean diameter, polydispersity and zeta potential requirements for hair care application. In addition to that, the particles are potentially useful for encapsulation of bioactives and also for the development of more efficient formulations than the free compounds ones / Mestrado / Desenvolvimento de Processos Biotecnologicos / Mestre em Engenharia Química

?rea de concentra??o: Ci?ncias farmac?uticas. / Data de aprova??o ausente. / Disponibiliza??o do conte?do parcial, conforme Termo de Autoriza??o no trabalho. / Submitted by Jos? Henrique Henrique (jose.neves@ufvjm.edu.br) on 2016-12-20T19:20:11Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) sara_pacelli_sousa_marcial_parcial.pdf: 166236 bytes, checksum: c01c4f087337cd82c64b06b90a1cc4dc (MD5) / Approved for entry into archive by Rodrigo Martins Cruz (rodrigo.cruz@ufvjm.edu.br) on 2017-01-17T18:55:36Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) sara_pacelli_sousa_marcial_parcial.pdf: 166236 bytes, checksum: c01c4f087337cd82c64b06b90a1cc4dc (MD5) / Made available in DSpace on 2017-01-17T18:55:36Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) sara_pacelli_sousa_marcial_parcial.pdf: 166236 bytes, checksum: c01c4f087337cd82c64b06b90a1cc4dc (MD5) Previous issue date: 2016 / Funda??o de Amparo ? Pesquisa do Estado de Minas Gerais (FAPEMIG) / O paclitaxel (PTX) ? um agente quimioter?pico que tem uma importante fun??o no tratamento de v?rios tipos de c?ncer, especialmente o c?ncer de mama. No entanto, a baixa solubilidade do PTX em meio aquoso (coeficiente de parti??o log = 3,96) representa uma limita??o para a administra??o intravenosa. A formula??o convencional do PTX cont?m uma alta concentra??o de Cremofor-EL? (derivado polietoxilado do ?leo de r?cino), o qual induz significante toxicidade, restringindo sua utiliza??o cl?nica. A encapsula??o do PTX em sistema de libera??o de f?rmacos pode melhorar a absor??o e aumentar a sua efic?cia terap?utica. Neste estudo, tr?s diferentes nanossistemas lip?dicos contendo PTX, nanopart?culas lip?dicas s?lidas (NLS), nanoemuls?o (NE) e carreadores lip?dicos nanoestruturados (CLN) foram preparados e as propriedades f?sico-qu?micas e a atividade citotoxicidade in vitro foram avaliadas. Em rela??o ao di?metro m?dio, o CLN branco mostrou valor de di?metro aproximadamente 2 e 1,7 vezes menor que os obtidos para NLS e NE, respectivamente. A presen?a de PTX levou a um aumento significativo no di?metro das part?culas em todos os sistemas avaliados, exceto no NE. Al?m disso, o aumento da concentra??o do f?rmaco (0,01% para 0,025%) produziu um aumento do di?metro para a prepara??o de CLN. Todas as formula??es com PTX mostraram ?ndice de polidispers?o superior a 0,3, exceto para NE-PTX na concentra??o do f?rmaco igual a 0,01% (p/v). Valores negativos de potencial zeta foram observados para todas as formula??es avaliadas. CLN-PTX foi o sistema mais est?vel ap?s armazenado por 30 dias a 4 ?C. O estudo de citotoxicidade nas linhagens celulares de c?ncer de mama (MDA-MB-231 e MCF-7) demonstrou atividade citot?xica mais pronunciada para CLN-PTX do que para o PTX livre em ambos as linhagens celulares do tumor. Baseado nesses resultados, CLN-PTX parece ser uma ferramenta potencial para o tratamento do c?ncer de mama. / Disserta??o (Mestrado) ? Programa de P?s-gradua??o em Ci?ncias Farmac?uticas, Universidade Federal dos Vales do Jequitinhonha e Mucuri, [2016]. / Paclitaxel (PTX) is a chemotherapeutic agent that plays an important role in the treatment of several types of human cancer, especially breast cancer. However, the low solubility of PTX in aqueous medium (partition coefficient log of 3.96) represents a barrier for intravenous administration. The conventional PTX formulation contains a high concentration of Cremophor-EL? (polyethoxylated castor oil), which is associated with significant toxicities restricting its clinical use. The encapsulation of the PTX in drug delivery systems could improve the uptake and increase its therapeutic efficacy. In this study, three different lipid nanosystems containing PTX, solid lipid nanoparticle (SLN), nanoemulsion (NE), and nanostructured lipid carrier (NLC) were prepared, and the physicochemical properties and in vitro cytotoxic activity were evaluated. Concerning the mean diameter, NLC blank showed diameter values approximately 2 and 1.7-fold lower than those obtained for SLN and NE, respectively. The presence of PTX leads to a significant increase in the particle diameter in all systems evaluated, except NE. In addition, increases in drug concentration (0.01% to 0.025%) produced an enhanced diameter for NLC preparation. All formulations containing PTX showed PI higher than 0.3, except for NE-PTX at drug concentration equal to 0.01% (w/v). Negative zeta potential values were observed in all formulations evaluated. NLC-PTX was the system more stable after storage for 30 days at 4 oC. The cytotoxicity studies on breast cancer cell lines (MDA-MB-231 and MCF-7) demonstrated cytotoxic activity more pronounced for NCL-PTX than for free PTX for both tumor cell lines. Thus, the results showed that NCL-PTX seems to be a potential tool for the treatment of breast cancer.

Les lipides « switch » - bascules - appartiennent à la famille des matériaux sensibles à un stimulus. Quand ces lipides bascules sont incorporés aux nanoparticules lipidiques (LNP), ils permettent la délivrance contrôlée grâce à un changement de conformation activé par une baisse de pH. Des expériences précédentes avaient démontré que les LNP bascules ont transfecté le petits ARN interférents (siRNA) in vitro et in vivo, silençant la protéine fluorescente verte (GFP) et la protéine hépatique Facteur VII, respectivement. La double administration de micro ARN (miRNA) et d'agent anticancéreux melphalan a également été réalisée par les LNP bascule sur un modèle de rétinoblastome murin. Ces résultats prometteurs nous ont encouragé à élargir les applications de LNP bascules en tant que vecteur de siRNA. De plus, le mécanisme par lequel les LNP bascules induisent la déstabilisation de la membrane et la libération de matériaux encapsulé au milleu acide reste obscur. La compréhension de ce mécanisme est cruciale pour cerner les avantages et les limites des LNP bascules, pour proposer des futures applications et pour prévenir leur toxicité. Dans ce mémoire, nous avons comme objectif d’évaluer le potentiel des LNP bascules pour le traitement du cancer. Nous avons évalué les LNP bascules comme vecteur de livraison du siRNA ciblant l'une des protéines cancéreuses les plus spécifiques découvertes à ce jour, la survivine. En parallèle, nous avons étudié le comportement biophysique des membranes contenant des lipides bascules dans des vésicules de taille micromètrique. Dans la première étude, nous avons démontré que les LNP bascules ont permis le silençage de la survivine dans une gamme de lignées cellulaires cancéreuses (poumon, cervical, ovaire, sein, côlon, rétinoblastome). Dans les cellules du rétinoblastome humain (Y79), nous avons examiné plusieurs agents cytotoxiques utilisés en clinique quant à leur synergie avec le silençage de la survivine: melphalan, topotécan, téniposide et carboplatine. Le prétraitement avec les LNP chargées de siRNA-survivine a amélioré de manière synergique la cytotoxicité du carboplatine et du melphalan mais dans une moindre mesure celle du topotécan et du téniposide. Cet effet était spécifique aux cellules cancéreuses car les cellules saines (ARPE.19) n'exprimaient pas de survivine. L'inhibition de la survivine par silençage de siRNA s'est révélée plus spécifique et moins dommageable pour les cellules saines (ARPE.19) que le YM155, un inhibiteur moléculaire de la survivine. Dans la deuxième étude, nous avons observé par microscopie confocale que les lipides bascules induisaient rapidement le stress, la fission et une courbure positive dans les membranes des vésicules unilamellaires géantes lorsqu'elles étaient exposées à des conditions acides. La dynamique de la membrane a été confirmée par des expériences de diffusion dynamique de la lumière (DLS) et de fuite de calcéine. Ces phénomènes ont également été observés lorsque des lipides bascules ont été incorporés dans une membrane hybride polymère/lipide, fournissant des propriétés sensibles au pH aux vésicules hybrides. À notre connaissance, c'est la première fois qu'une vésicule hybride sensible au pH est reportée. Nos résultats corroborent l'applicabilité des LNP bascules en tant qu'agents de vectorisation des siRNA pour le traitement du cancer grâce au silençage de la survivine, en particulier comme adjuvant à la chimiothérapie. L'investigation biophysique a révélé que les lipides bascules agissent sur la fluidité de la membrane, en particulier à pH acide. Cette sélectivité en pH garantit leur biocompatibilité à pH neutre ainsi que la libération efficace et rapide de leur cargo à pH acide. La compatibilité avec les vésicules hybrides polymère/lipide ouvre de nouvelles applications au niveau de vésicules biomimétiques et l'administration de médicaments. / Cationic switchable lipids belong to the class of stimuli-responsive materials. When incorporated in lipid nanoparticles (LNP), switchable LNP promote pH-triggered delivery of payload based on a molecular switch mechanism. Previous studies have demonstrated that switchable LNP successfully delivered small interferring RNA (siRNA) in vitro and in vivo, promoting the silencing of a reporter Green Fluorescencen Protein (GFP) protein and liver-produced factor VII, respectively. Dual delivery of micro RNA (miRNA) and anticancer agent melphalan was also achieved through switchable LNP in a retinoblastoma rat model. These promising results encouraged us to enlarge the applications of switchable LNP as siRNA carrier. Moreover, the mechanism whereby switchable LNP mediate acid-triggered membrane destabilization and, thus, payload release remains elusive. Understanding this mechanism is crucial to draw the advantages and limitations of switchable LNP, and to tailor their future applications and prevent their potential toxicity. In this dissertation, we aimed to further understand the potential of switchable LNP for cancer treatment. We assessed switchable LNP as a siRNA delivery carrier by targeting one of the most specific cancer protein discovered to date, survivin. Meanwhile, we investigated the biophysical behavior of switchable-lipid containing membranes in micron-sized vesicles. In the first study, we demonstrated that switchable LNP efficiently silenced survivin in a range of cancer cell line models (lung, cervical, ovary, breast, colon, retinoblastoma). In retinoblastoma (RB) cells (Y79), several clinically used cytotoxic agents were screened for their synergy with survivin silencing: melphalan, topotecan, Teniposide, and carboplatin. Pretreatment with LNP loaded with siRNA targeted against survivin synergistically enhanced the cytotoxicity of carboplatin and melphalan but in lesser extent topotecan and teniposide. This effect was specific to cancer cells since healthy cells (ARPE.19) did not express survivin. Survivin inhibition through siRNA silencing revealed more specific and less damageable for healthy cells (ARPE.19) than a molecular approach, such as YM155. In the second study, we observed by confocal microscopy that switchable lipids rapidly induced stress, fission, and positive curvature in giant unilamellar vesicles’ membranes when submitted to acidic conditions. The membrane dynamics was confirmed by dynamic light scattering and calcein leakage experiments. Remarkably, these phenomena were also observed when switchable lipids were embedded into a hybrid polymer/lipid membrane, providing pH-sensitive properties to hybrid vesicles. To the best of our knowledge, this is the first time a pH-sensitive hybrid vesicle is reported. Our findings corroborate with the applicability of switchable LNP as siRNA delivery agents for cancer treatment through survivin silencing, especially as an adjuvant to chemotherapy. The biophysical investigation revealed that the switchable lipids act on the membrane fluidity, specifically at acidic pH. This pH selectivity guarantees their biocompatibility at neutral pH as well as its efficient and quick release of their cargo at acidic pH. Their compatibility with hybrid polymer/lipid vesicles opens new applications in biomimetic vesicles and drug delivery.