Emerging carrier‐free nanosystems based on molecular self‐assembly of pure drugs for cancer therapy

Abstract

The potential toxicity of nanocarrier excipients and complicated preparation technologies have impeded the clinical application of nanomedicine. Recently, pure drug‐assembled nanosystems (PDANS) have been widely investigated, due to the unique self‐assembly characteristics of pure drug molecules. PDANS provides a facile nanoplatform for developing carrier‐free nanomedicine. Herein, the recent trends in PDANS for cancer therapy are outlined. First, the emerging strategies to develop single pure drug‐based nanoassemblies are discussed. Second, co‐assembly of two or more pure drugs for efficient combination therapy is overviewed. Then, the functional self‐assembly of non‐cytotoxic agents in tumor sites is presented. Finally, the rational design and self‐assembly mechanisms of these unique nanoplatforms are highlighted.

Carrier-free nanodrugs for safe and effective cancer treatment

“…Anti-cancer nanodrugs with combinational PTT are also explored due to the aforementioned benefits. Indocyanine green (ICG) is the only FDA approved PTT agent, and is a promising candidate in self-assembly with anti-cancer drugs, due to its hydrophilic sulphate and hydrophobic indole skeletons [88]. For these reasons, a variety of anti-cancer nanodrugs conjugated with ICG and its derivatives (IR820, IR780 iodide) were reported.…”

“…cytotoxic T lymphocyte-associated antigen 4 (CAR T) and programmed death/ligand 1(PD-1/L1) to enable T cells. Tumor environment is usually immune suppressed and crucial responses such as T cell activation and antigen presentation are inhibited [88]. For these reasons, eight new immunomodulatory drugs based on the blockage of PD-1/L1 and CAR T cell therapy were approved by FDA from 2014 to 2018.…”

“…Carrier-free nanodrugs increases the half-life of anti-cancer drugs, remaining stable in systemic circulation and overcoming rapid clearance [88]. Representative examples on how long anti-cancer drugs remain in circulation are shown in Table 3.…”

Molecularly engineered carrier-free co-delivery nanoassembly for self-sensitized photothermal cancer therapy

“…Series of organic photothermal agents have been found to exert antitumor activity by converting the near-infrared (NIR) light into tumor-localized heat [ 10 , 11 ]. Moreover, fluorescence characteristics in most photosensitizers (PSs) endows them a natural advantage in real-time tumor imaging and therapeutic monitoring [ 12 – 14 ]. In other words, PTT represents a versatile therapeutic regimen for image-guided precision cancer treatment [ 6 , 15 – 18 ].…”

“…Over the past few decades, multitudinous nano-vehicles have been designed for simultaneous co-encapsulation and co-delivery of two or more different drugs. However, these conventional co-delivery nanocarriers still have many drawbacks, such as low encapsulating or co-loading efficiency, inconvenient regulation of drug proportions, and inconsistency drug release caused by the affinity difference between carrier materials and different drugs [ 12 , 32 ]. Hence, there’s an urge need to develop more efficient co-delivery nanoplatforms.…”