Engineering microrobots for targeted cancer therapies from a medical perspective

Systemic chemotherapy remains the backbone of many cancer treatments. Due to its untargeted nature and the severe side effects it can cause, numerous nanomedicine approaches have been developed to overcome these issues. However, targeted delivery of therapeutics remains challenging. Engineering microrobots is increasingly receiving attention in this regard. Their functionalities, particularly their motility, allow microrobots to penetrate tissues and reach cancers more efficiently. Here, we highlight how different microrobots, ranging from tailor-made motile bacteria and tiny bubble-propelled microengines to hybrid spermbots, can be engineered to integrate sophisticated features optimised for precision-targeting of a wide range of cancers. Towards this, we highlight the importance of integrating clinicians, the public and cancer patients early on in the development of these novel technologies

Advanced medical micro-robotics for early diagnosis and therapeutic interventions

Recent technological advances in micro-robotics have demonstrated their immense potential for biomedical applications. Emerging micro-robots have versatile sensing systems, flexible locomotion and dexterous manipulation capabilities that can significantly contribute to the healthcare system. Despite the appreciated and tangible benefits of medical micro-robotics, many challenges still remain. Here, we review the major challenges, current trends and significant achievements for developing versatile and intelligent micro-robotics with a focus on applications in early diagnosis and therapeutic interventions. We also consider some recent emerging micro-robotic technologies that employ synthetic biology to support a new generation of living micro-robots. We expect to inspire future development of micro-robots toward clinical translation by identifying the roadblocks that need to be overcome

Iron-based magnetic nanosystems for diagnostic imaging and drug delivery : towards transformative biomedical applications

The advancement of biomedicine in a socioeconomically sustainable manner while achieving efficient patient-care is imperative to the health and well-being of society. Magnetic systems consisting of iron based nanosized components have gained prominence among researchers in a multitude of biomedical applications. This review focuses on recent trends in the areas of diagnostic imaging and drug delivery that have benefited from iron-incorporated nanosystems, especially in cancer treatment, diagnosis and wound care applications. Discussion on imaging will emphasise on developments in MRI technology and hyperthermia based diagnosis, while advanced material synthesis and targeted, triggered transport will be the focus for drug delivery. Insights onto the challenges in transforming these technologies into day-to-day applications will also be explored with perceptions onto potential for patient-centred healthcare

Zwitterionic materials for biomedical applications

La resposta del nostre cos als biomaterials suposa una gran obstacle per la efectivitat de múltiples teràpies basades en biomaterials. Accionats per la absorció inespecífica de biomolècules a la superfície del material, barreres com el sistema immune o les superfícies mucoses eliminen els materials del cos, evitant que arribin al seu destí i realitzin la seva funció. Els materials zwitteriònics han emergit en els últims anys com a materials antiadherents prometedors per a superar les mencionades barreres. Tot i que molts sistemes han utilitzat els materials zwitteriònics com a recobriments, les seves propietats úniques de superhidrofilicitat i versatilitat química suggereixen múltiples beneficis en utilitzar-los com a material principal. Aquí, dos sistemes diferents basats en materials zwitteriònics són presentats. En primer lloc una plataforma de alliberament de fàrmac antiadherent basat en copolímers de bloc amfifílics (CBA) és desenvolupada. Els CBAs zwitteriònics són sintetitzats i optimitzats perquè s’auto-organitzin en nanopartícules zwitteriòniques. Les propietats antiadherents d’aquestes nanopartícules es demostren, al igual que el seu potencial per a esdevenir un sistema d’alliberament de fàrmac oral. Seguidament, el sistema s’utilitza com a portador per a fàrmacs contra la malària i el càncer. Les nanopartícules mostren internalització en eritròcits infectats per Plasmòdium, i nanopartícules carregades amb curcumina demostren la seva eficàcia contra la malària in vitro. S’observa absorció oral de polímer i curcumina in vivo utilitzant un model de ratolí, indicant el potencial del sistema per a esdevenir una teràpia oral contra la malària. Quan s’optimitza el sistema per la teràpia contra el càncer, nanopartícules carregades de Paclitaxel exhibeixen activitat anti-cancerígena en models in vitro de cèl·lules canceroses. En segon lloc, microrobots zwitteriònics no-immunogènics que poden evitar el reconeixement per el sistema immune són introduïts. Es desenvolupa una fotoresistència zwitteriònica per a la microimpressió de microrobots zwitteriònics a través de la polimerització de dos fotons amb una ample funcionalització: propietats mecàniques variables, anti-bioadhesió i propietats no-immunogèniques, funcionalització per a la actuació magnètica, encapsulació de biomolècules i modificació superficial per a l’alliberament de fàrmac. Els robots invisibles eviten que els macròfags del sistema immune els detectin després d’una inspecció exhaustiva (de més de 90 hores), fet que no s’ha aconseguit fins el moment en cap sistema microrobòtic. Aquests materials zwitteriònics versàtils eliminen un dels grans obstacles en el desenvolupament de microrobots biocompatibles, i serviran com una caixa d’eines de materials no-immunogènics per a crear robots biomèdics i altres dispositius per a la bioenginyeria i per a aplicacions biomèdiques.La respuesta de nuestro cuerpo a los biomateriales supone un gran obstáculo para la efectividad de múltiples terapias basadas en los biomateriales. Accionados por la absorción de biomoléculas en la superficie del material, barreras como el sistema inmune o las superficies mucosas eliminan los materiales del cuerpo, evitando que lleguen a su destino y realicen su función. Los materiales zwitteriónicos han emergido en los últimos años como materiales antiadherentes prometedores para superar las barreras mencionadas. Aunque muchos sistemas utilizan materiales zwitteriónicos como recubrimientos, sus propiedades únicas de superhidrofilicidad i versatilidad química sugieren múltiples beneficios en utilizarlos como material principal. Aquí, dos sistemas basados en materiales zwitteriónicos son presentados. En primer lugar, una plataforma para la liberación de fármaco antiadherente basada en copolímeros de bloque amfifílicos (CBA) es desarrollada. Los CBA zwitteriónicos son sintetizados y optimizados para que se auto-organicen en nanopartículas zwitteriónicas. Las propiedades antiadherentes de estas nanopartículas son probadas, al igual que su potencial para convertirse en un sistema oral de liberación de fármaco. Seguidamente, el sistema se utiliza como portador para fármacos animalarios y anticancerígenos. Las nanopartículas muestran internalización en eritrocitos infectados por Plasmodio, y nanopartículas cargadas con curcumina demuestran su eficacia contra la malaria in vitro. Se observa la absorción oral de polímero y curcumina in vivo utilizando un modelo de ratón, indicando el potencial del sistema para convertirse en una terapia oral contra malaria. Cuando se optimiza el sistema para la terapia contra el cáncer, las nanopartículas cargadas con Paclitaxel exhiben actividad anticancerígena en modelos in vitro de células cancerosas. En segundo lugar, microrobots zwitteriónicos no-inmunológicos que pueden evitar el reconocimiento por parte del sistema inmune son introducidos. Se desarrolla una fotoresisténcia zwitteriónica para la microimpresión de microrobots zwitteriónicos a través de la polimerización de dos fotones con una amplia funcionalización: propiedades mecánicas variables, anti-bioadhesión i propiedades no-inmunogénicas, funcionalización para la actuación magnética, encapsulación de biomoléculas i modificación superficial para la liberación de fármaco. Los robots invisibles evitan que los macrófagos del sistema inmune innato los detecten después de una inspección exhaustiva (de más de 90 horas), hecho que no se ha conseguido hasta la fecha por ningún sistema microrobótico. Estos materiales zwitteriónicos versátiles eliminan uno de los grandes obstáculos en el desarrollo de microrobots biocompatibles, y servirán como una caja de herramientas de materiales no-inmunogénicos para crear robots biomédicos y otros dispositivos para la bioingeniería y para las aplicaciones biomédicas.Body response to biomaterials suppose a major roadblock for the effectiveness of multiple biomaterial-based therapies. Triggered by unspecific absorption of biomolecules in the material surface, barriers such as immune system or mucosal surfaces clear foreign materials from the body, preventing them to reach their target and perform their function. Zwitterionic materials have emerged in the last years as promising antifouling materials to overcome the mentioned barriers. Although many systems have used zwitterionic materials as coatings, the unique properties of superhydrophilicity and chemical versatility suggest multiple benefits of using zwitterionic polymers as bulk materials. Here, two different systems based on zwitterionic materials are presented. In first place, an antifouling drug delivery platform based on zwitterionic amphiphilic polymers (ABC) is developed. Zwitterionic ABCs are synthetized and optimized to self-assemble in zwitterionic nanoparticles. The antifouling properties of zwitterionic nanoparticles are proved, together with their potential to become an oral drug delivery system. Next, the system is used as a drug carrier for antimalarial and anticancer drugs. Nanoparticles show internalization in Plasmodium infected erythrocytes, and curcumin-loaded nanoparticles prove their antimalarial efficacy in vitro. Oral absorption of polymer and curcumin is also observed in vivo using mice model, indicating the potential of this system to become oral therapy against malaria. When optimizing the system for anticancer therapy, Paclitaxel-loaded nanoparticles exhibit anticancer activity in in vitro cancer cell models. Second, non‐immunogenic stealth zwitterionic microrobots that avoid recognition from immune cells are introduced. Zwitterionic photoresist are developed for the 3D microprinting of zwitterionic hydrogel microrobots through 2-photon polymerization with ample functionalization: tunable mechanical properties, anti-biofouling and non-immunogenic properties, functionalization for magnetic actuation, encapsulation of biomolecules, and surface functionalization for drug delivery. Stealth microrobots avoid detection by macrophage cells of the innate immune system after exhaustive inspection (> 90 h), which has not been achieved in any microrobotic platform to date. These versatile zwitterionic materials eliminate a major roadblock in the development of biocompatible microrobots, and will serve as a toolbox of non-immunogenic materials for medical microrobot and other device technologies for bioengineering and biomedical applications

Advanced medical micro-robotics for early diagnosis and therapeutic interventions

Recent technological advances in micro-robotics have demonstrated their immense potential for biomedical applications. Emerging micro-robots have versatile sensing systems, flexible locomotion and dexterous manipulation capabilities that can significantly contribute to the healthcare system. Despite the appreciated and tangible benefits of medical micro-robotics, many challenges still remain. Here, we review the major challenges, current trends and significant achievements for developing versatile and intelligent micro-robotics with a focus on applications in early diagnosis and therapeutic interventions. We also consider some recent emerging micro-robotic technologies that employ synthetic biology to support a new generation of living micro-robots. We expect to inspire future development of micro-robots toward clinical translation by identifying the roadblocks that need to be overcome

Magnetic systems for cancer immunotherapy

Immunotherapy is a rapidly developing area of cancer treatment due to its higher specificity and potential for greater efficacy than traditional therapies. Immune cell modulation through the administration of drugs, proteins, and cells can enhance antitumoral responses through pathways that may be otherwise inhibited in the presence of immunosuppressive tumors. Magnetic systems offer several advantages for improving the performance of immunotherapies, including increased spatiotemporal control over transport, release, and dosing of immunomodulatory drugs within the body, resulting in reduced off-target effects and improved efficacy. Compared to alternative methods for stimulating drug release such as light and pH, magnetic systems enable several distinct methods for programming immune responses. First, we discuss how magnetic hyperthermia can stimulate immune cells and trigger thermoresponsive drug release. Second, we summarize how magnetically targeted delivery of drug carriers can increase the accumulation of drugs in target sites. Third, we review how biomaterials can undergo magnetically driven structural changes to enable remote release of encapsulated drugs. Fourth, we describe the use of magnetic particles for targeted interactions with cellular receptors for promoting antitumor activity. Finally, we discuss translational considerations of these systems, such as toxicity, clinical compatibility, and future opportunities for improving cancer treatment. &nbsp;</p

Magnetogels: prospects and main challenges in biomedical applications

Drug delivery nanosystems have been thriving in recent years as a promising application in therapeutics, seeking to solve the lack of specificity of conventional chemotherapy targeting and add further features such as enhanced magnetic resonance imaging, biosensing and hyperthermia. The combination of magnetic nanoparticles and hydrogels introduces a new generation of nanosystems, the magnetogels, which combine the advantages of both nanomaterials, apart from showing interesting properties unobtainable when both systems are separated. The presence of magnetic nanoparticles allows the control and targeting of the nanosystem to a specific location by an externally applied magnetic field gradient. Moreover, the application of an alternating magnetic field (AMF) not only allows therapy through hyperthermia, but also enhances drug delivery and chemotherapeutic desired effects, which combined with the hydrogel specificity, confer a high therapeutic efficiency. Therefore, the present review summarizes the magnetogels properties and critically discusses their current and recent biomedical applications, apart from an outlook on future goals and perspectives.This work was funded by the Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Funding of CF-UM-UP (UID/FIS/04650/2013) and CQUM (UID/QUI/00686/2016). S.R.S.V. acknowledges FCT for a research grant under UID/FIS/04650/2013 funding.info:eu-repo/semantics/publishedVersio