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Nanopartículas como sistemas de transporte de RNAs regulatórios em terapias para o cancro oral: avanços e aplicações clínicas – uma revisão narrativa
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| Projeto de pós-graduação_21802 | 1.26 MB | Adobe PDF |
Orientador(es)
Resumo(s)
O carcinoma oral de células escamosas (OSCC) representa a forma mais prevalente de cancro oral, caracterizando-se por elevada agressividade biológica, invasão local precoce, risco de metastização regional e alta taxa de recorrência. O diagnóstico continua frequentemente a ocorrer em fases avançadas da doença, o que condiciona a eficácia terapêutica e contribui para a elevada morbilidade. As abordagens convencionais — cirurgia, quimioterapia e radioterapia — associam-se a efeitos adversos severos e sequelas permanentes, muitas vezes com impacto funcional e estético irreversível. Além disso, a resistência terapêutica, tanto primária como adquirida, limita significativamente a resposta ao tratamento e a sobrevivência global dos pacientes. Neste contexto, as nanomedicinas emergem como uma estratégia inovadora para ultrapassar estas limitações, sobretudo através do uso de nanopartículas projetadas para a entrega dirigida de terapias baseadas em RNA regulatório. Estes RNAs — incluindo microRNAs (miRNA), small interfering RNAs (siRNA) e long non-coding RNAs (lncRNA) — atuam ao nível pós-transcricional, modulando seletivamente a expressão de oncogenes ou genes supressores tumorais. A sua aplicação terapêutica tem sido dificultada por problemas de estabilidade, imunogenicidade e falta de especificidade, desafios que podem ser eficazmente superados pela associação a nanopartículas inteligentes. As nanopartículas descritas nos estudos analisados incluem estruturas lipídicas, poliméricas, metálicas, híbridas e biológicas (como exossomas), com propriedades adaptadas ao microambiente tumoral. Estas plataformas demonstraram capacidade para aumentar a estabilidade sistémica dos RNAs, promover acumulação seletiva no tumor, e libertação da carga em resposta a estímulos específicos como pH, glutationa ou enzimas tumorais. Diversos estudos in vivo revelaram efeitos antitumorais significativos — incluindo redução do volume tumoral, inibição da angiogénese, apoptose tumoral e reversão de resistência a fármacos clássicos como a cisplatina — confirmando o potencial desta abordagem como alternativa terapêutica eficaz e de menor toxicidade para o tratamento do OSCC.
Oral squamous cell carcinoma (OSCC) is the most prevalent form of oral cancer, characterized by high biological aggressiveness, early local invasion, regional lymph node metastasis, and a high recurrence rate. Diagnosis often occurs at advanced stages, limiting therapeutic efficacy and contributing to substantial morbidity. Conventional treatment strategies — surgery, chemotherapy, and radiotherapy — are associated with severe side effects and frequently result in permanent functional and aesthetic sequelae. Furthermore, both intrinsic and acquired therapeutic resistance significantly compromise treatment response and overall patient survival. In this scenario, nanomedicine has emerged as a promising strategy to overcome these limitations, particularly through the use of nanoparticles designed for the targeted delivery of regulatory RNA-based therapies. These RNAs — including microRNAs (miRNAs), small interfering RNAs (siRNAs), and long non-coding RNAs (lncRNAs) — act at the post-transcriptional level, selectively modulating oncogene or tumor suppressor gene expression. However, their therapeutic application is challenged by issues related to instability, immunogenicity, and lack of specificity — hurdles that can be effectively addressed by encapsulation within intelligent nanoparticle platforms. The nanoparticles described in the reviewed studies include lipid-based, polymeric, metallic, hybrid, and biologically-derived systems (such as exosomes), engineered with features adapted to the tumor microenvironment. These nanocarriers have demonstrated the ability to enhance the systemic stability of regulatory RNAs, promote tumor-selective accumulation, and trigger controlled release in response to specific stimuli such as pH, glutathione, or tumor-associated enzymes. Multiple in vivo studies have shown marked antitumor effects — including tumor volume reduction, inhibition of angiogenesis, induction of apoptosis, and reversal of resistance to conventional drugs such as cisplatin — reinforcing the potential of this strategy as an effective and less toxic alternative for OSCC treatment.
Oral squamous cell carcinoma (OSCC) is the most prevalent form of oral cancer, characterized by high biological aggressiveness, early local invasion, regional lymph node metastasis, and a high recurrence rate. Diagnosis often occurs at advanced stages, limiting therapeutic efficacy and contributing to substantial morbidity. Conventional treatment strategies — surgery, chemotherapy, and radiotherapy — are associated with severe side effects and frequently result in permanent functional and aesthetic sequelae. Furthermore, both intrinsic and acquired therapeutic resistance significantly compromise treatment response and overall patient survival. In this scenario, nanomedicine has emerged as a promising strategy to overcome these limitations, particularly through the use of nanoparticles designed for the targeted delivery of regulatory RNA-based therapies. These RNAs — including microRNAs (miRNAs), small interfering RNAs (siRNAs), and long non-coding RNAs (lncRNAs) — act at the post-transcriptional level, selectively modulating oncogene or tumor suppressor gene expression. However, their therapeutic application is challenged by issues related to instability, immunogenicity, and lack of specificity — hurdles that can be effectively addressed by encapsulation within intelligent nanoparticle platforms. The nanoparticles described in the reviewed studies include lipid-based, polymeric, metallic, hybrid, and biologically-derived systems (such as exosomes), engineered with features adapted to the tumor microenvironment. These nanocarriers have demonstrated the ability to enhance the systemic stability of regulatory RNAs, promote tumor-selective accumulation, and trigger controlled release in response to specific stimuli such as pH, glutathione, or tumor-associated enzymes. Multiple in vivo studies have shown marked antitumor effects — including tumor volume reduction, inhibition of angiogenesis, induction of apoptosis, and reversal of resistance to conventional drugs such as cisplatin — reinforcing the potential of this strategy as an effective and less toxic alternative for OSCC treatment.
Descrição
Palavras-chave
Cancro oral Nanomedicina RNA regulatório Nanopartícula Carcinoma de células espinhosas oral Silenciamento genético Oral cancer Nanomedicine Regulatory RNA Squamous cell carcinoma Gene silencing