Targeted drug delivery to melanoma Liu, Qi; Das, Manisit; Liu, Yun ...
Advanced drug delivery reviews,
03/2018, Volume:
127
Journal Article
Peer reviewed
Melanoma derived from melanocytes is the most aggressive genre of skin cancer. Although the considerable advancement in the study of human cancer biology and drug discovery, most advanced melanoma ...patients are inevitably unable to be cured. With the emergence of nanotechnology, the use of nano-carriers is widely expected to alter the landscape of melanoma treatment. In this review, we will discuss melanoma biology, current treatment options, mechanisms behind drug resistance, and nano-based solutions for effective anti-cancer therapy, followed by challenges and perspectives in both pre-clinical and clinical settings.
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This review discussed about the green biosynthesis of magnetite nanoparticles (Fe3O4-NPs) and the biomedical applications, which mainly focus on the targeted anticancer drug delivery. Fe3O4-NPs have ...been studied and proved that Fe3O4-NPs can be used in various fields of application, due to “superparamagnetic” property that Fe3O4-NPs possessed. In targeted drug delivery system, drug loaded Fe3O4-NPs can accumulate at the tumor site by the aid of external magnetic field. This can increase the effectiveness of drug release to the tumor site and vanquish cancer cells without harming healthy cells. In order to apply Fe3O4-NPs in human body, Fe3O4-NPs have to be biocompatible and biodegradable to minimize the toxicity. So, green biosynthesis plays a crucial role as the biosynthesized Fe3O4-NPs is safe to be consumed by human because the materials used are from biological routes, such as plant extract and natural polymer. However, biosynthesis using plant extract is the most popular among them all as plant extract can act as both reducing and stabilizing agents in the synthesizing process of nanoparticles. This approach is not merely simple, yet economic and less waste production, which is environmental friendly. Several biomedical applications of Fe3O4-NPs are included in this review, but anticancer drug delivery study is discussed in detail. The criteria for Fe3O4-NPs to be used as drug delivery vehicle are discussed so as to study the optimum condition of Fe3O4-NPs in drug delivery application. Many researches showed the promising results of Fe3O4-NPs in treating cancer cells via in vitro study. Hence, this review is significant which summarize the vital points of Fe3O4-NPs in targeted anticancer drug delivery system. Conclusions have been made according to the literature reviewed and some points of view were proposed for future study.
Mesoporous silica nanoparticles functionalized with peptides are developed for sequential drug delivery. The RGD peptide is used for vasculature/cell membrane targeting and the TAT peptide for ...nuclear targeting. Using this delivery strategy, a tumor in a murine xenograft model is successfully regressed.
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Breast cancer treatment can be challenging, but a targeted drug delivery system (DDS) has the potential to make it more effective and reduce side effects. This study presents a novel ...nanotherapeutic targeted DDS developed through the self-assembly of an amphiphilic di-block copolymer to deliver the chemotherapy drug SN38 specifically to breast cancer cells. The vehicle was constructed from the PHPMA-b-PEAMA diblock copolymer synthesized via RAFT polymerization. A single emulsion method was then used to encapsulate SN38 within nanoparticles (NPs) formed from the PHPMA-b-PEAMA copolymer. The AS1411 DNA aptamer was covalently bonded to the surface of the micellar NPs, producing a targeted DDS. Molecular dynamics (MD) simulation studies were also performed on the di block polymeric system, demonstrating that SN38 interacted well with the di block. The in vitro results demonstrated that AS1411- decorated SN38-loaded HPMA NPs were highly toxic to breast cancer cells while having a minimal effect on non-cancerous cells. Remarkably, in vivo studies elucidated the ability of the targeted DDS to enhance the antitumor effect of SN38, suppressing tumor growth and improving survival rates compared to free SN38.
The cell nucleus‐targeted delivery of therapeutic agents plays a critical role in cancer therapy, since the biological target of many anticancer therapeutics is the cell nucleus. However, multiple ...physiological barriers limit the delivery efficiency of free drugs, resulting in unsatisfactory therapeutic effects. Herein, thioketal crosslinked polyphosphoester‐based nanoparticles with a tumor acidity (pHe)‐sensitive transactivator of transcription (TAT) peptide (DA‐masked TAT‐decorating reactive oxygen species (ROS)‐sensitive Ce6/DOX‐loaded hyperbranched nanoparticles (DTRCD)) are explored for cascade nucleus‐targeted drug delivery. Following administration, DTRCD experiences prolonged circulation by masking the targeting effect of its TAT peptide and then achieves enhanced tumor cell uptake and improved translocation into the perinuclear region by reactivating the TAT targeting capability in tumor tissue. Subsequently, ROS generated by DTRCD under 660 nm laser not only disrupts the nuclear membrane to allow entry into the nuclei but also triggers intracellular release of the payload in the nuclei. As evidenced by in vivo experiments, such pHe/photo dual‐sensitive polymeric nanocarriers offer remarkable therapeutic effects, efficiently suppressing tumor growth. This multistage cascade nucleus‐targeted drug delivery concept provides new avenues to develop nucleus‐targeted drug delivery systems.
Cascade pHe/photo dual‐sensitive 2,3‐dimethylmaleic anhydride‐masked transactivator of transcription (TAT)‐decorating reactive oxygen species (ROS)‐sensitive Ce6/doxorubicin‐loaded hyperbranched nanoparticles (DTRCD) are explored for direct nucleus‐targeted drug delivery. The TAT targeting effect of DTRCD is masked to prolonged circulation and reactivated at tumor tissue to enhance cell uptake and translocation into the perinuclear region. Subsequently, DTRCD generates ROS under illumination to disrupt the nuclear membrane to allow nanoparticle entry and trigger intranuclear drug release.
Advances in nanomedicine, including early cancer detection, targeted drug delivery, and personalized approaches to cancer treatment are on the rise. For example, targeted drug delivery systems can ...improve intracellular delivery because of their multifunctionality. Novel endogenous-based and exogenous-based stimulus-responsive drug delivery systems have been proposed to prevent the cancer progression with proper drug delivery. To control effective dose loading and sustained release, targeted permeability and individual variability can now be described in more-complex ways, such as by combining internal and external stimuli. Despite these advances in release control, certain challenges remain and are identified in this research, which emphasizes the control of drug release and applications of nanoparticle-based drug delivery systems. Using a multiscale and multidisciplinary approach, this study investigates and analyzes drug delivery and release strategies in the nanoparticle-based treatment of cancer, both mathematically and clinically.
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•Nanoparticles have great potential to improve the efficacy of drug delivery.•The drug-release rate and mechanism significantly increase nano-based drug delivery system efficacy.•Stimulus-responsive nanocarriers (external and internal) promise better control of drug release.•Mathematical models usefully explicate and predict clinical translation.•Combining internal and external nanocarrier stimuli enables controlled targeted drug delivery.
As a non-invasive dosage form, transdermal targeted drug delivery system avoids first-pass effect, improves and maintains blood drug concentration, reduces gastrointestinal stimulation, eliminates ...adverse reactions, and increases patient compliance. However, due to the barrier function of the stratum corneum of the skin, only a few drugs are suitable for transdermal administration, and most drugs cannot reach effective therapeutic concentrations through the skin after transdermal administration. The key to solve the problem is to improve the drugs transdermal permeability and prolong the retention time. The main advantages of nanosuspension are including high drug loading, small particle size, large specific surface area, easy industrial production. Therefore, the nanosuspension for transdermal target delivery has strong adhesion and penetration with skin, is not easy to be removed, and significantly improves the pharmacokinetic characteristics and bioavailability of water insoluble drugs. The influencing factors for transdermal delivery, nanosuspension technology for improving the skin penetration, as well as challenges and future perspectives was reviewed in this article. Nanosuspension can promote the transdermal target absorption of drugs and improve the bioavailability of local drug delivery, which present a good clinical application prospect. This review could be provide a reference for the nanosuspension technology in the transdermal target drug delivery.
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Exosomes are nanoscale extracellular vesicles that have become pivotal in advancing targeted drug delivery strategies for cancer therapy. In this study, we conducted a comparative analysis of the ...intracellular targeting capabilities of differently shaped exosomes, including milk exosome nanorods (MR), ginger exosome nanorods (GR), and cancer cell exosome nanorods (HR), compared to their spherical counterparts. Our observations revealed that exosome nanorods demonstrated effective and sustained targeting of the endoplasmic reticulum (ER) within cancer cells, while exosome nanospheres were captured within lysosomes. Building on this principle, we chose milk-derived exosomes (mExo) for the in vivo research, engineering the surface of MR with folate to enhance their tumor-targeting efficacy. We demonstrated the effective accumulation of these folate-modified MR (FMR) around the ER in cancer cells, as validated in both orthotopic colorectal cancer (CRC) tissues and human CRC biopsy samples. Furthermore, when loaded with curcumin (Cur), the FMR@Cur exhibited remarkable efficacy in suppressing tumors in orthotopic CRC mouse models. This effect is attributed to the targeted delivery of FMR@Cur to the ER, leading to enhanced ER-stress induced apoptosis. Overall, our study underscores the pivotal role of shape engineering in exosome-mediated drug delivery, offering novel insights and paving the way for innovative strategies to enhance the precision of intracellular drug targeting in cancer therapy.
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•Exosome shape affects their fate: exosome nanorods target the endoplasmic reticulum, while nanospheres go to lysosomes.•Shape-mediated targeting boosts exosome nanorods’ retention in the endoplasmic reticulum, avoiding rapid cellular clearance.•Exosome nanorods target the endoplasmic reticulum in colorectal cancer cells, mouse models, and clinical biopsy biopsies.•Curcumin-loaded exosome nanorods show superior anticancer effects and biocompatibility in a colorectal cancer mouse model.
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Liposomal delivery systems have significantly enhanced the efficacy and safety of chemotherapeutic agents compared to free (non-liposomal) formulations. Liposomes are vesicles made up ...of lipophilic bilayer and a hydrophilic core which provides perfect opportunity for their application as transport vehicle for various therapeutic and diagnostic agents. Doxorubicin is the most exploited chemotherapeutic agent for evaluation of different liposomal applications, as its physicochemical properties permit high drug entrapment and easy remote loading in pre-formulated liposomes. Pegylated liposomal doxorubicin clinically approved and, on the market, Doxil®, exemplifies the benefits offered upon the surface modification of liposome with polyethylene glycol. This unique formulation prolonged the drug residence time in the circulation and increased accumulation of doxorubicin in tumor tissue via passive targeting (enhanced permeability and retention effect). However, there is ample scope for further improvement in the efficiency of targeting tumors by coupling biological active ligands onto the liposome surface to generate intelligent drug delivery systems. Small biomolecules such as peptides, fraction of antibodies and carbohydrates have the potential to target receptors present on the surface of the malignant cells. Hence, active targeting of malignant cells using functionalised nanocarrier (liposomes encapsulated with doxorubicin) have been attempted which is reviewed in this article.
Drug Delivery
In article number 2207787, Can Yang Zhang, Wei Tao, and co‐workers review the recent advances in living‐leukocyte‐mediated drug delivery. Due to the targeted response to the ...inflammatory environment, leukocytes (e.g., neutrophils, macrophages, and lymphocytes) have great potential as targeted carriers for drug delivery and are expected to bring breakthroughs in the precise treatment of cancer and inflammation‐related diseases.
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