Current cancer nanomedicines can only mitigate adverse effects but fail to enhance therapeutic efficacies of anticancer drugs. Rational design of next-generation cancer nanomedicines should aim to enhance their therapeutic efficacies. Taking this into account, this review first analyzes the typical cancer-drug-delivery process of an intravenously administered nanomedicine and concludes that the delivery involves a five-step CAPIR cascade and that high efficiency at every step is critical to guarantee high overall therapeutic efficiency. Further analysis shows that the nanoproperties needed in each step for a nanomedicine to maximize its efficiency are different and even opposing in different steps, particularly what the authors call the PEG, surface-charge, size and stability dilemmas. To resolve those dilemmas in order to integrate all needed nanoproperties into one nanomedicine, stability, surface and size nanoproperty transitions (3S transitions for short) are proposed and the reported strategies to realize these transitions are comprehensively summarized. Examples of nanomedicines capable of the 3S transitions are discussed, as are future research directions to design high-performance cancer nanomedicines and their clinical translations.

Rational Design of Cancer Nanomedicine: Nanoproperty Integration and Synchronization.

Non-viral vectors are simple in theory but complex in practice. Apart from intra cellular and extracellular barriers, number of other challenges also needs to be overcome in order to increase the effectiveness of non-viral gene transfer. These barriers are categorized as production, formulation and storage. No one-size-fits-all solution to gene delivery, which is why in spite of various developments in liposome, polymer formulation and optimization, new compounds are constantly being proposed and investigated. In this review, we will see in detail about various types of non-viral vectors highlighting promising development and recent advances that had improved the non-viral gene transfer efficiency of translating from "Bench to bedside".

Non viral vectors in gene therapy- an overview.

In vivo delivery of miRNAs for cancer therapy: challenges and strategies.

Nonviral cancer gene therapy: Delivery cascade and vector nanoproperty integration.

Bioengineered and biohybrid bacteria-based systems for drug delivery.

A key end goal of gene delivery research is to develop clinically relevant vectors that can be used to combat elusive diseases such as AIDS. Despite promising engineering strategies, efficiency and ultimately gene modulation efficacy of nonviral vectors have been hindered by numerous in vitro and in vivo barriers that have resulted in subviral performance. In this perspective, we concentrate on the gene delivery barriers associated with the two most common classes of nonviral vectors, cationic-based lipids and polymers. We present the existing delivery barriers and summarize current vector-specific strategies to overcome said barriers.

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Overcoming Nonviral Gene Delivery Barriers: Perspective and Future

Genetic vaccines offer a treatment opportunity based upon successful gene delivery to specific immune cell modulators. Driving the process is the vector chosen for gene cargo packaging and subsequent delivery to antigen-presenting cells (APCs) capable of triggering an immune cascade. As such, the delivery process must successfully navigate a series of requirements and obstacles associated with the chosen vector and target cell. In this work, we present the development and assessment of a hybrid gene delivery vector containing biological and biomaterial components. Each component was chosen to design and engineer gene delivery separately in a complimentary and fundamentally distinct fashion. A bacterial (Escherichia coli) inner core and a biomaterial [poly(beta-amino ester)]-coated outer surface allowed the simultaneous application of molecular biology and polymer chemistry to address barriers associated with APC gene delivery, which include cellular uptake and internalization, phagosomal escape, and intracellular cargo concentration. The approach combined and synergized normally disparate vector properties and tools, resulting in increased in vitro gene delivery beyond individual vector components or commercially available transfection agents. Furthermore, the hybrid device demonstrated a strong, efficient, and safe in vivo humoral immune response compared with traditional forms of antigen delivery. In summary, the flexibility, diversity, and potential of the hybrid design were developed and featured in this work as a platform for multivariate engineering at the vector and cellular scales for new applications in gene delivery immunotherapy.

https://www.pnas.org/content/pnas/111/34/12360.full.pdf

Hybrid biosynthetic gene therapy vector development and dual engineering capacity

Improvements to bacterial vectors have resulted in nonviral gene therapy vehicles that are easily prepared and can achieve high levels of transfection efficacy. However, these vectors are plagued b...

Polymyxin B Treatment Improves Bactofection Efficacy and Reduces Cytotoxicity

Bactofection offers a gene delivery option particularly useful in the context of immune modulation. The bacterial host naturally attracts recognition and cellular uptake by antigen presenting cells (APCs) as the initial step in triggering an immune response. Moreover, depending on the bacterial vector, molecular biology tools are available to influence and/or overcome additional steps and barriers to effective antigen presentation. In this work, molecular engineering was applied using Escherichia coli as a bactofection vector. In particular, the bacteriophage ΦX174 lysis E (LyE) gene was designed for variable expression across strains containing different levels of lysteriolysin O (LLO). The objective was to generate a bacterial vector with improved attenuation and delivery characteristics. The resulting strains exhibited enhanced gene and protein release and inducible cellular death. In addition, the new vectors demonstrated improved gene delivery and cytotoxicity profiles to RAW264.7 macrophage APCs.

Snehal Rane

Papers

Overcoming Nonviral Gene Delivery Barriers: Perspective and Future

Hybrid biosynthetic gene therapy vector development and dual engineering capacity

Polymyxin B Treatment Improves Bactofection Efficacy and Reduces Cytotoxicity

Improved Escherichia coli Bactofection and Cytotoxicity by Heterologous Expression of Bacteriophage ΦX174 Lysis Gene E.