Cell-penetrating peptides (CPPs) are short peptides (fewer than 30 amino acids) that have been predominantly used in basic and preclinical research during the last 30 years. Since they are not only capable of translocating themselves into cells but also facilitate drug or CPP/cargo complexes to translocate across the plasma membrane, they have potential applications in the disease diagnosis and therapy, including cancer, inflammation, central nervous system disorders, otologic and ocular disorders, and diabetes. However, no CPPs or CPP/cargo complexes have been approved by the US Food and Drug Administration (FDA). Many issues should be addressed before translating CPPs into clinics. In this review, we summarize recent developments and innovations in preclinical studies and clinical trials based on using CPP for improved delivery, which have revealed that CPPs or CPP-based delivery systems present outstanding diagnostic therapeutic delivery potential.

/pdf/cell-penetrating-peptides-in-diagnosis-and-treatment-of-1ldodep9at.pdf

Cell-Penetrating Peptides in Diagnosis and Treatment of Human Diseases: From Preclinical Research to Clinical Application

Cancer is currently ineffectively treated using therapeutic drugs, and is also able to resist drug action, resulting in increased side effects following drug treatment. A novel therapeutic strategy against cancer cells is the use of anticancer peptides (ACPs). The physicochemical properties, amino acid composition and the addition of chemical groups on the ACP sequence influences their conformation, net charge and orientation of the secondary structure, leading to an effect on targeting specificity and ACP‑cell interaction, as well as peptide penetrating capability, stability and efficacy. ACPs have been developed from both naturally occurring and modified peptides by substituting neutral or anionic amino acid residues with cationic amino acid residues, or by adding a chemical group. The modified peptides lead to an increase in the effectiveness of cancer therapy. Due to this effectiveness, ACPs have recently been improved to form drugs and vaccines, which have sequentially been evaluated in various phases of clinical trials. The development of the ACPs remains focused on generating newly modified ACPs for clinical application in order to decrease the incidence of new cancer cases and decrease the mortality rate. The present review could further facilitate the design of ACPs and increase efficacious ACP therapy in the near future.

/pdf/anticancer-peptide-physicochemical-property-functional-1n99d44vww.pdf

Anticancer peptide: Physicochemical property, functional aspect and trend in clinical application (Review)

Systemic delivery of peptides by the oral route: Formulation and medicinal chemistry approaches.

Polymeric microneedles for controlled transdermal drug delivery

Various therapeutic techniques have been studied for treating cancer precisely and effectively, such as targeted drug delivery, phototherapy, tumor-specific catalytic therapy, and synergistic therapy, which, however, evoke numerous challenges due to the inherent limitations of these therapeutic modalities and intricate biological circumstances as well. With the remarkable advances of nanotechnology, nanoplatform-based cascade engineering, as an efficient and booming strategy, has been tactfully introduced to optimize these cancer therapies. Based on the designed nanoplatforms, pre-supposed cascade processes could be triggered under specific conditions to generate/deliver more therapeutic species or produce stronger tumoricidal effects inside tumors, aiming to achieve cancer therapy with increased anti-tumor efficacy and diminished side effects. In this review, the recent advances in nanoplatform-based cascade engineering for cancer therapy are summarized and discussed, with an emphasis on the design of smart nanoplatforms with unique structures, compositions and properties, and the implementation of specific cascade processes by means of endogenous tumor microenvironment (TME) resources and/or exogenous energy inputs. This fascinating strategy presents unprecedented potential in the enhancement of cancer therapies, and offers better controllability, specificity and effectiveness of therapeutic functions compared to the corresponding single components/functions. In the end, challenges and prospects of such a burgeoning strategy in the field of cancer therapy will be discussed, hopefully to facilitate its further development to meet the personalized treatment demands.

Nanoplatform-based cascade engineering for cancer therapy

Cell-penetrating peptide: a means of breaking through the physiological barriers of different tissues and organs

Immunotherapy that harnesses the human immune system to fight cancer has received widespread attention and become a mainstream strategy for cancer treatment. Cancer immunotherapy not only eliminates primary tumors but also treats metastasis and recurrence, representing a major advantage over traditional cancer treatments. Recently with the development of nanotechnology, there exists much work applying nanomaterials to cancer immunotherapy on the basis of their excellent physiochemical properties, such as efficient tissue-specific delivery function, huge specific surface area, and controllable surface chemistry. Consequently, nanotechnology holds significant potential in improving the efficacy of cancer immunotherapy. Nanotechnology-based immunotherapy mainly manifests its inhibitory effect on tumors via two different approaches: one is to produce an effective anti-tumor immune response during tumorigenesis, and the other is to enhance tumor immune defense ability by modulating the immune suppression mechanism in the tumor microenvironment. With the success of tumor immunotherapy, understanding the interaction between the immune system and smart nanomedicine has provided vigorous vitality for the development of cancer treatment. This review highlights the application, progress, and prospect of nanomedicine in the process of tumor immunoediting and also discusses several engineering methods to improve the efficiency of tumor treatment.

Nanotechnology for Boosting Cancer Immunotherapy and Remodeling Tumor Microenvironment: The Horizons in Cancer Treatment.

Graphene-based nanomaterials (GBNMs) have great potential in drug delivery and photothermal therapy owing to their unique physicochemical properties. However, inferior water solubility and biocompatibility related issues greatly restricted their further applications. Herein, to rectify the obstructive problems, we prepared uniform and smaller sized graphene oxide (GO) nanosheets (∼85 nm) via a modified Hummers' method, which exhibited significantly improved hemocompatibility compared to random large sized GO nanosheets prepared by a common method. Then, we grafted unfractionated heparin (UFH) onto reduced graphene oxide (rGO) covalently using adipic acid dihydrazide (ADH) as a linker to fabricate biocompatible nanocomposites for the cellular delivery of curcumin (Cur). The novel nanocomposites showed quite a small size of 42 nm in average lateral dimension and exhibited a significantly stronger photothermal effect than GO nanosheets. Besides, in vitro cell experiments verified that the potential anticancer efficacy of Cur-loaded vehicles and cytotoxicity of rGO-UFH/Cur against MCF-7 and A549 cells could be further enhanced under 808 nm irradiation, suggesting the possibility of combinational chemotherapy and photothermal therapy. Moreover, consistent with the in vitro sustained drug release performance, an in vivo pharmacokinetics study also indicated that the retention time of Cur could be significantly prolonged when loaded on rGO-UFH nanocomposites than in free Cur solution. Notably, we firstly discussed the interaction between rGO and Cur, and demonstrated the meliorative biocompatibility of uniform rGO compared to GRO via a molecular dynamics simulation (MD) study. Thus, the in vitro, in vivo and computational study demonstrated that the small sized rGO-UFH nanocomposites had wide application prospects as drug delivery vehicles.

Heparin-reduced graphene oxide nanocomposites for curcumin delivery: in vitro, in vivo and molecular dynamics simulation study.

Photo-triggered self-destructive ROS-responsive nanoparticles of high paclitaxel/chlorin e6 co-loading capacity for synergetic chemo-photodynamic therapy.

Jiangkang Xu

Papers

Cell-penetrating peptide: a means of breaking through the physiological barriers of different tissues and organs

Nanotechnology for Boosting Cancer Immunotherapy and Remodeling Tumor Microenvironment: The Horizons in Cancer Treatment.

Heparin-reduced graphene oxide nanocomposites for curcumin delivery: in vitro, in vivo and molecular dynamics simulation study.

Photo-triggered self-destructive ROS-responsive nanoparticles of high paclitaxel/chlorin e6 co-loading capacity for synergetic chemo-photodynamic therapy.

Redox-responsive hyaluronic acid-based nanoparticles for targeted photodynamic therapy/chemotherapy against breast cancer