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Brain cancers are some of the most complex diseases to treat, despite the numerous advances science has made in cancer chemotherapy and research. One of the key obstacles to identifying potential cures for this disease is the difficulty in emulating the complexity of the brain and the surrounding microenvironment to understand potential therapeutic approaches. This paper discusses some of the most important in vitro, in vivo, and microfluidic brain tumor models that aim to address these challenges.

Abstract Liposomes are the most successful nanoparticles used to date to load and deliver chemotherapeutic agents to cancer cells. They are nano-sized vesicles made up of phospholipids, and targeting moieties can be added to their surfaces for the active targeting of specific tumors. Furthermore, Ultrasound can be used to trigger the release of the loaded drugs by disturbing their phospholipid bilayer structure. In this study, we have prepared pegylated liposomes using four types of phospholipids with similar saturated hydrocarbon tails including a phospholipid with no head group attached to the phosphate head (DPPA) and three other phospholipids with different head groups attached to their phosphate heads (DPPC, DPPE and DPPG). The prepared liposomes were conjugated to the monoclonal antibody trastuzumab (TRA) to target the human epidermal growth factor receptor 2 (HER2) overexpressed on HER2-positive cancer cells (HER2+). We have compared the response of the different formulations of liposomes when triggered with low-frequency ultrasound (LFUS) and their cellular uptake by the cancer cells. The results showed that the different formulations had similar size, polydispersity, and stability. TRA-conjugated DPPC liposomes showed the highest sensitivity to LFUS. On the other hand, incubating the cancer cells with TRA-conjugated DPPA liposomes triggered with LFUS showed the highest uptake of the loaded calcein by the HER2+ cells.

Over the past few decades, notable advancements have been made in the field of transdermal drug delivery systems (TDDSs), presenting a promising alternative to conventional oral drug administration. This comprehensive review aims to enhance understanding of this method by examining various transdermal techniques, the skin’s role as a barrier to TDDS, factors affecting skin diffusion, and current challenges in TDDSs. The primary focus of this analysis centers on TDDSs utilizing hydrogels. A thorough exploration of hydrogel fundamentals, encompassing structure, properties, and synthesis, is provided to underscore the importance of hydrogels as carriers in transdermal drug delivery. The concluding section delves into strategies for hydrogel-based drug delivery, addressing challenges and exploring future directions.

Targeted liposomes enable the delivery of encapsulated chemotherapeutics to tumours by targeting specific receptors overexpressed on the surfaces of cancer cells; this helps in reducing the systemic side effects associated with the cytotoxic agents. Upon reaching the targeted site, these liposomes can be triggered to release their payloads using internal or external triggers. In this study, we investigate the use of low-frequency ultrasound as an external modality to trigger the release of a model drug (calcein) from non-targeted and targeted pegylated liposomes modified with cyclic arginine–glycine–aspartate (cRGD). Liposomes were exposed to sonication at 20-kHz using three different power densities (6.2, 9, and 10 mW/cm2). Our results showed that increasing the power density increased calcein release from the sonicated liposomes. Moreover, cRGD conjugation to the surface of the liposomes rendered cRGD-liposomes more susceptible to ultrasound compared to the non-targeted liposomes. cRGD conjugation was also found to increase cellular uptake of calcein by human colorectal carcinoma (HCT116) cells which were further enhanced following sonicating the cells with low-frequency ultrasound (LFUS).

Abstract Targeted liposomes are designed to target specific receptors overexpressed on the surfaces of cancer cells. This technique ensures site-specific drug delivery to reduce undesirable side effects while enhancing the efficiency of the encapsulated therapeutics. Upon reaching the tumor site, these liposomes can be triggered to release their content in a controlled manner using ultrasound (US). In this study, drug release from pegylated calcein-loaded liposomes modified with transferrin (Tf) and triggered with US was evaluated. Low-frequency ultrasound at 20-kHz using three different power densities (6.2 mW/cm2, 9 mW/cm2 and 10 mW/cm2) was found to increase calcein release. In addition, transferrin-conjugated pegylated liposomes (Tf-PEG liposomes) were found to be more sonosensitive compared to the non-targeted (control) liposomes. Calcein uptake by HeLa cells was found to be significantly higher with the Tf-PEG liposomes compared to the non-targeted control liposomes. This uptake was further enhanced following the exposure to low-frequency ultrasound (at 35 kHz). These findings show that targeted liposomes triggered with US have promising potential as a safe and effective drug delivery platform.

A number of promising nano-sized particles (nanoparticles) have been developed to conquer the limitations of conventional chemotherapy. One of the most promising methods is stimuli-responsive nanoparticles because they enable the safe delivery of the drugs while controlling their release at the tumor sites. Different intrinsic and extrinsic stimuli can be used to trigger drug release such as temperature, redox, ultrasound, magnetic field, and pH. The intracellular pH of solid tumors is maintained below the extracellular pH. Thus, pH-sensitive nanoparticles are highly efficient in delivering drugs to tumors compared to conventional nanoparticles. This review provides a survey of the different strategies used to develop pH-sensitive nanoparticles used in cancer therapy.

Quantum dots (QDs) are a promising tool to detect and monitor tumors. However, their small size allows them to accumulate in large quantities inside the healthy cells (in addition to the tumor cells), which increases their toxicity. In this study, we synthesized stealth liposomes encapsulating hydrophilic graphene quantum dots and triggered their release with ultrasound with the goal of developing a safer and well-controlled modality to deliver fluorescent markers to tumors. Our results confirmed the successful encapsulation of the QDs inside the core of the liposomes and showed no effect on the size or stability of the prepared liposomes. Our results also showed that low-frequency ultrasound is an effective method to release QDs encapsulated inside the liposomes in a spatially and temporally controlled manner to ensure the effective delivery of QDs to tumors while reducing their systemic toxicity.