Biological Based Nanomedicines

**10**

*Current and Future Aspects of Nanomedicine*

Nanoparticles in the clinic: An update. Bioengineering & Translational Medicine [Internet]. 2019;**4**(3):1-16.

[8] Choi YH, Han H-K. Nanomedicines: Current status and future perspectives

Pharmaceutical Investigation [Internet].

in aspect of drug delivery and pharmacokinetics. Journal of

2018;**48**(1):43-60. DOI: 10.1007/

s40005-017-0370-4

[1] Anselmo AC, Mitragotri S.

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**13**

**Chapter 2**

**Abstract**

cargo when in a tumor.

**1. Introduction**

Phage Capsids as Gated,

Delivery Vehicles

Long-Persistence, Uniform Drug

Over the last 25 years, cancer therapies have improved survivorship. Yet, metastatic cancers remain deadly. Therapies are limited by inadequate targeting. Our goal is to develop a new drug delivery vehicle (DDV)-based strategy that improves targeting of drug delivery to solid tumors. We begin with a capsid nanoparticle derived from bacteriophage (phage) T3, a phage that naturally has high persistence in murine blood. This capsid has gating capacity. For rapidly detecting loading in this capsid, here, we describe procedures of native agarose gel electrophoresis, coupled with fluorescence-based detection of loaded molecules. We observe the loading of two fluorescent compounds: the dye, GelStar, and the anticancer drug, bleomycin. The optimal emission filters were found to be orange and green, respectively. The results constitute a first milestone in developing a drug-loaded DDV that does not leak when in blood, but unloads its

*Philip Serwer, Elena T. Wright and Cara B. Gonzales*

**Keywords:** agarose gel electrophoresis, bacteriophage T3, bleomycin, buoyant density centrifugation, capsid impermeability, GelStar

specificity, then overall efficiency is 99% [100 × (1.0 − 0.2<sup>3</sup>

(2) tumor cell evolution of drug resistance is minimized.

Current therapies for cancerous tumors suffer from both toxic secondary effects and the development by the tumor of drug resistance. These effects usually block therapy for metastatic cancers, the cause of 90% of cancer deaths [1–5]. For solving these problems, our first thesis is that the best strategy is to increase tumor specificity of anticancer drug delivery in several, *independent* stages. If, for example, three stages are used and each stage is 80% efficient (20% nonefficient) in increasing

dosages to tumors can be raised 100× without changing toxicity and, therefore,

The primary alternative is to continue testing chemotherapies [6–8], immunotherapies [9–11] and radiotherapies [12–14] that have tumor-specificity determined at one independent stage. This one stage is often cellular DNA replication, which is more rapid and, therefore, more drug- and radiation-sensitive, in cancerous cells than it is in healthy cells. One-stage strategies are >100 years old for immunotherapy and radiotherapy. Chemotherapeutic agents typically used are over 50 years old [8]. Even major effort has not produced systematic therapies for metastatic cancer.

)]. In this case, (1) drug
