Intracellularly Degradable, Self‐Assembled Amphiphilic Block Copolycurcumin Nanoparticles for Efficient In Vivo Cancer Chemotherapy

Abstract

Chemotherapy is widely used in various cancer treatments. However, current cancer chemotherapy has a major limitation: lacking of specific targeting ability. As a result, it kills both cancerous and healthy cells, causing severe adverse side-effects and toxicity to patients which limits the dose regime and allows tumour to gain resistance. One approach to address this problem is the development of nanoscale drug delivery systems (NDDSs) which can exploit characteristic properties of tumour, such as the enhanced permeation and retention (EPR) effect, [1] and over-expressed cell-surface receptors, [2] to achieve targeted delivery. [3] Despite significant research achievements, most of the current NDDSs, especially those in clinical trials or usage, e.g. drug encapsulated lipids vesicles or polymer micelles, [4] polymerdrug conjugates, and albumin-based nanoparticles, [5] mostly rely on passive targeting and generally lack the ability of active targeting. Moreover, drugs are mostly physically encapsulated or entrapped into the NDDSs, where drug release is mainly achieved via passive diffusion, making it difficult to achieve controlled release, a vital property for high therapeutic 2 efficacy. As a result, most of the drug payloads may have been released before reaching the target sites, leading to reduced therapeutic efficacy and causing adverse side-effects.Furthermore, most NDDSs also suffer from drawbacks such as low drug loading (e.g.antibody-drug conjugates) and/or burst release (e.g. micelles/liposomes). To date, none of the current NDDSs can satisfy all of the requirements of an "idea NDDS" outlined by Langer et al. [3a] To make best use of the advantages of current NDDSs (passive and active targeting delivery to tumour) and overcome their drawbacks (unnecessary and even harmful on-way drug release before entering tumour cells and/or only a small quantity of drugs together with the nano-carriers entering tumour cells) due to the physical incorporation or encapsulation of drugs in NDDSs, which often leads to uncontrolled drug release via diffusion, we take a new approach to prepare NDDSs which is based on so-called poly(active pharmaceutical ingredient) (PAPI) strategy where the APIs are incorporated into an intracellular cleavable polymer backbone (not physically incorporated in drug carriers) in combination with selfassembly characteristics of amphiphilic block copolymers. Here PAPI is defined as a polymer prepared by polycondensation of an API or its derivative having the same or similar bioactivity as a co-or sole-monomer. Considerable advantages here are that the physicalchemical properties of the PAPIs can be readily tailored by changing co-monomers or via chemical modifications. The PAPIs can be further made into various NDDSs where the API release can be controlled via stimuli triggered polymer degradation, overcoming the drawback of un-controlled, diffusion based drug release character commonly experienced in physically incorporated systems. In principle, any drug molecules/derivatives containi...

Highly Fluorescent Ribonuclease-A-Encapsulated Lead Sulfide Quantum Dots for Ultrasensitive Fluorescence in Vivo Imaging in the Second Near-Infrared Window

“…Figure 4 shows the immunofluorescent analysis of neuronal cells treated with PBS, RNase-A@PbS Qdots, and Pb(OAc) 2 for 24 h. The nuclei stained with Hoechst 33342 appear in blue while the cell bodies, dendrites, and axons are stained with monoclonal anti-β-tubulin antibodies which emit red. 38 Similar to the healthy control, the neurons incubated with a high dose of the Qdots (∼1 μM, equivalent to total Pb 2+ concentration = 824 μM) are found to form a neurite network without any observable debris, suggesting minimal neurotoxicity. On the contrary, the neurite growth and network formation are downright inhibited by 0.5 μM Pb(OAc) 2 , at a concentration that is >1600-fold lower than the total lead content contained in the Qdot sample.…”

Sodium cholate-enhanced polymeric micelle system for tumor-targeting delivery of paclitaxel

“…Amount of the PTX in micelles Weight of the micelles = × 100 0% (1) EE% Amount of the PTX in micelles Total amount of PTX added = × × 100% (2) critical micelle concentration…”

“…1,2 Paclitaxel (PTX) is one of the best antineoplastic agents in the taxane family and has shown significant clinical activity against a wide variety of tumors, including ovarian cancer, lung cancer, and breast cancer. 3 Most clinically available formulations are aspecific and have huge disadvantages, such as serious side effects, low stability, fast drug release, and lack of tumor-targeting capability.…”

PHB‐Based Gels as Delivery Agents of Chemotherapeutics for the Effective Shrinkage of Tumors

“…Doxorubicin (DOX) is a drug which contains quinone. It has been used to treat several types of cancer due to its excellent pharmaceutical activity . It achieves its therapeutic effects by intercalating with the DNA double helix, stabilizing DNA replication‐associated enzymes, such as topoisomerase, to inhibit the replication process .…”