Engineering Macrophages via Nanotechnology and Genetic Manipulation for Cancer Therapy

Macrophages play critical roles in tumor progression. In the tumor microenvironment, macrophages display highly diverse phenotypes and may perform antitumorigenic or protumorigenic functions in a context-dependent manner. Recent studies have shown that macrophages can be engineered to transport drug nanoparticles (NPs) to tumor sites in a targeted manner, thereby exerting significant anticancer effects. In addition, macrophages engineered to express chimeric antigen receptors (CARs) were shown to actively migrate to tumor sites and eliminate tumor cells through phagocytosis. Importantly, after reaching tumor sites, these engineered macrophages can significantly change the otherwise immune-suppressive tumor microenvironment and thereby enhance T cell-mediated anticancer immune responses. In this review, we first introduce the multifaceted activities of macrophages and the principles of nanotechnology in cancer therapy and then elaborate on macrophage engineering via nanotechnology or genetic approaches and discuss the effects, mechanisms, and limitations of such engineered macrophages, with a focus on using live macrophages as carriers to actively deliver NP drugs to tumor sites. Several new directions in macrophage engineering are reviewed, such as transporting NP drugs through macrophage cell membranes or extracellular vesicles, reprogramming tumor-associated macrophages (TAMs) by nanotechnology, and engineering macrophages with CARs. Finally, we discuss the possibility of combining engineered macrophages and other treatments to improve outcomes in cancer therapy.

A combined miR-34a and arsenic trioxide nanodrug delivery system for synergistic inhibition of HCC progression after microwave ablation

Background Microwave ablation (MWA) has become an alternative treatment for unresectable hepatocellular carcinoma (HCC), but it does not eliminate the risk of recurrence and metastasis after treatment. Recent studies have demonstrated that miR-34a presents decreased gene expression in residual tumours after ablation therapy and can increase the therapeutic effect of arsenic trioxide against HCC, which brings new opportunities for HCC treatment. Methods A pH-sensitive charge inversion material was used to construct a nanotargeted delivery system based on the synergistic effects of miR-34a and As2O3. We established in vitro and in vivo models of HCC microwave ablation and performed in-depth research on the dual-drug system to inhibit the rapid progression and induce pyroptosis in HCC cells after microwave ablation. Results The antitumour effects were enhanced with the dual-drug nanoparticles relative to the single-drug formulations, and the therapeutic efficacy of the nanoparticles was more significant in a weakly acidic environment. The dual-drug nanoparticles increased the N-terminal portion of GSDME and decreased the expression of Cyt-c and c-met. Conclusions Dual-drug nanoparticles may improve the therapeutic efficacy of HCC treatment after insufficient ablation through Cyt-c and GSDME-N and decrease the expression levels of c-met. These nanoparticles are expected to provide new treatment methods for residual HCC after MWA, prolong the survival of patients and improve their quality of life.

Targeting of Inhaled Therapeutics to the Small Airways: Nanoleucine Carrier Formulations

Current dry powder formulations for inhalation deposit a large fraction of their emitted dose in the upper respiratory tract where they contribute to off-target adverse effects and variability in lung delivery. The purpose of the current study is to design a new formulation concept that more effectively targets inhaled dry powders to the large and small airways. The formulations are based on adhesive mixtures of drug nanoparticles and nanoleucine carrier particles prepared by spray drying of a co-suspension of leucine and drug particles from a nonsolvent. The physicochemical and aerosol properties of the resulting formulations are presented. The formulations achieve 93% lung delivery in the Alberta Idealized Throat model that is independent of inspiratory flow rate and relative humidity. Largely eliminating URT deposition with a particle size larger than solution pMDIs is expected to improve delivery to the large and small airways, while minimizing alveolar deposition and particle exhalation.

Targeting of Inhaled Therapeutics to the Small Airways: Nanoleucine Carrier Formulations

Current dry powder formulations for inhalation deposit a large fraction of their emitted dose in the upper respiratory tract where they contribute to off-target adverse effects and variability in lung delivery. The purpose of current study is to design a new formulation concept that more effectively targets inhaled dry powders to the large and small airways. The formulations are based on adhesive mixtures of drug nanoparticles and nanoleucine carrier particles prepared by spray drying of a co-suspension of leucine and drug particles from a nonsolvent. The physicochemical and aerosol properties of the resulting formulations are presented. The formulations achieve 93% lung delivery in the Alberta Idealized Throat model that is independent of inspiratory flow rate and relative humidity. Largely eliminating URT deposition with a particle size larger than solution pMDIs is expected to improve delivery to the large and small airways, while minimizing alveolar deposition and particle exhalation.

A Review on Drug Delivery System for Tumor Therapy

In recent years, with the development of nanomaterials, the research of drug delivery systems has become a new field of cancer therapy. Compared with conventional antitumor drugs, drug delivery systems such as drug nanoparticles (NPs) are expected to have more advantages in antineoplastic effects, including easy preparation, high efficiency, low toxicity, especially active tumor-targeting ability. Drug delivery systems are usually composed of delivery carriers, antitumor drugs, and even target molecules. At present, there are few comprehensive reports on a summary of drug delivery systems applied for tumor therapy. This review introduces the preparation, characteristics, and applications of several common delivery carriers and expounds the antitumor mechanism of different antitumor drugs in delivery carriers in detail which provides a more theoretical basis for clinical application of personalized cancer nanomedicine in the future.