pH-Triggered Micelles for Tumor Delivery

Although selective tumor delivery of anticancer drugs has been sought by exploiting either passive targeting or by ligand-mediated targeting, a selective anticancer therapy remains an unmet medical need. Despite the advances which have been achieved by nanomedicines, nanosystems such as polymer-drug conjugates still miss the goal of clinical efficacy. In this study, we demonstrated that polymer-drug conjugates require a thoroughly chemical design and the right targeting agent/polymer ratio to be selective and effective towards cancer cells. In particular, two PEG conjugates carrying paclitaxel and targeted with different folic acid (FA)/PEG ratios (one or three) were investigated. The cytotoxicity study in positive (HT-29) and negative (HCT-15) FA receptor (FR)-cell lines demonstrated that the conjugates with one or three FAs were 4- or 28-fold more active in HT-29 cells, respectively. The higher activity of the 3-FA conjugate was confirmed by its strong impact on cell cycle arrest. Furthermore, FA targeting had a clear effect on migration and invasiveness of HT-29 cells, which were significantly reduced by both conjugates. Interestingly, the 3-FA conjugate showed also an improved pharmacokinetic profile in mice. The results of this study indicate that thorough investigations are needed to optimize and tune drug delivery and achieve the desired selectivity and activity towards cancer cells.

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Nanoparticles as Drug Delivery Systems of RNAi in Cancer Therapy

Molecules ◽

10.3390/molecules26082380 ◽

2021 ◽

Vol 26 (8) ◽

pp. 2380

Author(s):

Diedie Li ◽

Chengzhi Gao ◽

Meiyan Kuang ◽

Minhao Xu ◽

Ben Wang ◽

...

Keyword(s):

Drug Delivery ◽

Drug Delivery Systems ◽

Therapeutic Strategy ◽

Target Gene ◽

Treatment Approach ◽

Systemic Delivery ◽

Efficient Delivery ◽

Rnai Therapeutics ◽

Cellular Machinery ◽

Tumor Delivery

RNA interference (RNAi) can mediate gene-silencing by knocking down the expression of a target gene via cellular machinery with much higher efficiency in contrast to other antisense-based approaches which represents an emerging therapeutic strategy for combating cancer. Distinct characters of nanoparticles, such as distinctive size, are fundamental for the efficient delivery of RNAi therapeutics, allowing for higher targeting and safety. In this review, we present the mechanism of RNAi and briefly describe the hurdles and concerns of RNAi as a cancer treatment approach in systemic delivery. Furthermore, the current nanovectors for effective tumor delivery of RNAi therapeutics are classified, and the characteristics of different nanocarriers are summarized.

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Non-invasive Magnetic Resonance Imaging Follow-up of Sono-sensitive Liposome Tumor Delivery and Controlled Release After High-Intensity Focused Ultrasound

Ultrasound in Medicine & Biology ◽

10.1016/j.ultrasmedbio.2013.06.002 ◽

2013 ◽

Vol 39 (12) ◽

pp. 2342-2350 ◽

Cited By ~ 9

Author(s):

Robert Andrew Fowler ◽

Sigrid L. Fossheim ◽

Jean-Louis Mestas ◽

Jacqueline Ngo ◽

Emmanuelle Canet-Soulas ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Controlled Release ◽

Magnetic Resonance ◽

High Intensity ◽

Focused Ultrasound ◽

High Intensity Focused Ultrasound ◽

Resonance Imaging ◽

Non Invasive ◽

Tumor Delivery

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Pharmacologic Considerations in the Disposition of Antibodies and Antibody-Drug Conjugates in Preclinical Models and in Patients

Antibodies ◽

10.3390/antib8010003 ◽

2019 ◽

Vol 8 (1) ◽

pp. 3 ◽

Cited By ~ 9

Author(s):

Andrew T. Lucas ◽

Ryan Robinson ◽

Allison N. Schorzman ◽

Joseph A. Piscitelli ◽

Juan F. Razo ◽

...

Keyword(s):

Cytotoxic Agents ◽

Clinical Use ◽

Individual Agent ◽

Antibody Drug Conjugates ◽

Drug Conjugates ◽

Rational Development ◽

Patient Variables ◽

Tumor Delivery ◽

Agent Characteristics ◽

Antibody Drug

The rapid advancement in the development of therapeutic proteins, including monoclonal antibodies (mAbs) and antibody-drug conjugates (ADCs), has created a novel mechanism to selectively deliver highly potent cytotoxic agents in the treatment of cancer. These agents provide numerous benefits compared to traditional small molecule drugs, though their clinical use still requires optimization. The pharmacology of mAbs/ADCs is complex and because ADCs are comprised of multiple components, individual agent characteristics and patient variables can affect their disposition. To further improve the clinical use and rational development of these agents, it is imperative to comprehend the complex mechanisms employed by antibody-based agents in traversing numerous biological barriers and how agent/patient factors affect tumor delivery, toxicities, efficacy, and ultimately, biodistribution. This review provides an updated summary of factors known to affect the disposition of mAbs/ADCs in development and in clinical use, as well as how these factors should be considered in the selection and design of preclinical studies of ADC agents in development.

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