Making medicines survive the journey: how MUST researchers are tackling the biological barriers between a promising treatment and its effect

Making medicines survive the journey: how MUST researchers are tackling the biological barriers between a promising treatment and its effect

 

A promising treatment must do more than fight disease. Across 12 inventions, researchers are drawing on chemistry, RNA biology, immunology, pharmacology and materials science to tackle the barriers a medicine can encounter before it can do its job.

A medicine’s role might seem simple: enter the body, locate the disease, and act. However, the path from administering a promising treatment to achieving its desired effect can be complex. This challenge is not new; researchers have long examined the biological barriers affecting how medicines circulate, gather in diseased tissue, and reach their targets. For instance, a 2015 Nature Biotechnology perspective described drug delivery as a series of obstacles that therapeutic systems may need to overcome [1].

Recognizing these barriers is one step; discovering ways to surmount them is another. In 12 inventions from Macau University of Science and Technology researchers, multiple disciplines collaborate across various stages [2]–[13]. They pose a key question for therapeutic innovation: not only what can fight disease, but also what must occur beforehand to make that possible.

 

The journey begins with what we call a medicine

Before making any disclosures, researchers need to identify a promising candidate. Several inventions are investigating natural sources for potential therapeutic molecules. One invention describes a bi-magnolignan with a distinctive molecular structure and anticancer activity [2]. Another explores curcumenol for lung cancer treatment [3], and a third develops the cardiac glycoside 19-dihydrocalotoxin, examining its anti-tumor effects and capacity to inhibit HIF-1 [4]. The patent for this compound specifically claims its use against tumors and as an HIF-1 inhibitor.

Some inventions expand beyond small molecules to include RNA-based therapies. One U.S. patent investigates RNA extracted or derived from Taxus plants for cancer treatment [5], while another describes double-stranded RNA from Ganoderma lucidum targeting ovarian, rectal, and liver cancers [6]. Thus, the initial focus of this research can be either a newly discovered chemical structure or biological information encoded within RNA.

 

Surviving the trip, and finding the destination

Laboratory activity is just the initial step. Some therapeutic agents face challenges in transportation or cell entry, while others require precise control over their location and mode of action. One approach involves synthesizing sphingolipid compounds to create cationic liposomes characterized by high transfection efficiency, stability, and relatively low toxicity [7]. The same patent details co-delivery studies of paclitaxel and HIF-1α siRNA, linking drug delivery to efforts to mitigate tumor responses under hypoxic conditions. Materials science offers alternatives by combining carbon materials with copper metal-organic frameworks. One invention broadens this to a carbon–Cu-MOF platform [8], while another leverages graphdiyne’s large surface area and π-electron-rich structure to bind copper and facilitate Fenton-like ROS generation [9].

For inflammatory diseases, researchers have taken inspiration from cells involved in inflammation. One system integrates celastrol-loaded mesoporous silica, a ROS-responsive lipid layer, and an M2 macrophage membrane to target rheumatoid arthritis [10]. This membrane coating enhances localization to inflamed joints and speeds up drug release in high-ROS environments. Another invention employs activated neutrophil membranes around liposomes carrying leonurine and catalase [11]. Catalase reacts with hydrogen peroxide to produce oxygen, causing the carrier to disintegrate and release drugs faster as ROS levels increase. In this context, a hostile disease environment transforms from a barrier into a biological signal that guides treatment activation.

 

When disease fights back

Reaching the right tissue doesn’t guarantee success, as disease biology can influence cellular responses to treatment. One rheumatoid arthritis innovation targets ABCB5-mediated multidrug resistance, identifying sinomenine and its derivatives as ABCB5 inhibitors aimed at reversing resistance and enhancing treatment when combined with methotrexate [12]. Another RA invention focuses on NAV2, proposing the endogenous hydrogen-sulfide donor SPRC to suppress NAV2, reduce Wnt/β-catenin signalling, inflammatory proteins, and the aggressive behavior of synovial fibroblasts [13]. In cancer, HIF-1-related inventions [4], [7] address biological responses in oxygen-deprived tumor environments. Sometimes, improving treatment requires understanding how biology impedes progress, rather than simply seeking a more potent drug.

 

A medicine has more to overcome than the disease

None of these barriers are new, and no single invention solves the entire process. However, examining the 12 inventions reveals how researchers can intervene at different points. A complex molecule might create a new carrier, immune cells can provide guidance, and abnormal chemistry at a disease site can trigger drug release or be part of the attack. When cells resist existing medicines, understanding this resistance can uncover new therapeutic targets. This challenges the usual idea that failure is always due to a weak molecule; often, the journey ends not because of the agent but because of biological limitations. For patients, the goal remains clear: effective treatment. Achieving this often requires addressing challenges well before the medicine encounters the disease. Finding an initial promising candidate is just the start; understanding every obstacle it faces determines its ultimate success.

 

From research to application

Many of these inventions are in early or preclinical phases, yet their potential uses span therapeutic discovery, RNA delivery, nanomedicine, targeted drug delivery, and tackling treatment resistance. Industry partners seeking licensing, technology development, or research collaborations are encouraged to review the individual patents and explore opportunities to translate these innovations into practical solutions.

 

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References

[1] E. Blanco, H. Shen, and M. Ferrari, “Principles of nanoparticle design for overcoming biological barriers to drug delivery,” Nat. Biotechnol., vol. 33, no. 9, pp. 941–951, Sep. 2015, doi: 10.1038/nbt.3330.

[2] W. Ma et al., “一种联二厚朴脂素及其制备方法和应用 [A bi-magnolignan and its preparation method and application],” China Patent CN 115466237 B, Apr. 2, 2024.

[3] Q. Wu, X. Sui, R. Zhang, and X. Wang, “莪术烯醇在制备抗肺癌药物中的应用 [Application of curcumenol in preparing an anti-lung-cancer drug],” China Patent CN 113181166 B, Jan. 5, 2024.

[4] L. Bai, Z. Zheng, X. Zhou, G. Zhu, and Z. Jiang, “一种强心苷类化合物及其合成方法与应用 [A cardiac glycoside compound and its synthesis method and application],” China Patent CN 112194703 B, Aug. 3, 2021.

[5] Z.-H. Jiang, T.-M. Yan, and K.-Y. Cao, “Method and pharmaceutical composition for treating cancer,” U.S. Patent 11 149 271 B2, Oct. 19, 2021.

[6] Z. Jiang, F. Ren, K. Cao, and R. Gong, “双链 RNA 分子及其医药用途 [Double-stranded RNA molecules and pharmaceutical uses thereof],” China Patent CN 114875027 B, Sep. 24, 2024.

[7] Z. Jiang, L. Bai, T. Xu, X. Zhou, and Y. Guo, “鞘脂类化合物、含有鞘脂类化合物的脂质体和应用 [Sphingolipid compounds, liposomes containing the sphingolipid compounds, and applications],” China Patent CN 114933569 B, Jul. 23, 2024.

[8] W. Xie et al., “一种碳-铜金属有机框架纳米复合材料及其制备方法和应用 [Carbon–copper metal-organic-framework nanocomposite material, preparation method and application],” China Patent CN 115671311 A, Feb. 3, 2023.

[9] W. Xie et al., “一种石墨炔-铜金属有机框架复合纳米材料及其制备方法和仿生材料及其制备方法 [Graphdiyne–copper metal-organic-framework composite nanomaterial, its preparation method, and biomimetic material and preparation method],” China Patent CN 115845082 A, Mar. 28, 2023.

[10] X. Wang, Y. Xiao, and X. Zhang, “巨噬细胞膜包被 ROS 响应性仿生纳米递药系统、制备及应用 [Macrophage-membrane-coated ROS-responsive biomimetic nanodrug delivery system, preparation and application],” China Patent CN 119112839 A, Dec. 13, 2024.

[11] X. Wang, Y. Zhu, Z. Tang, and S. Meng, “一种 ROS 响应性仿生纳米递药系统、制备方法及应用 [ROS-responsive biomimetic nanodrug delivery system, preparation method and application],” China Patent CN 119097716 A, Dec. 10, 2024.

[12] J. Huang, L. Liu, W. Luo, C. Qiu, W. Zhang, and C. Xia, “ABCB5 抑制剂在制备多耐药性类风湿性关节炎治疗药物中的应用 [Application of ABCB5 inhibitors in preparing therapeutics for multidrug-resistant rheumatoid arthritis],” China Patent CN 115260098 B, Jun. 4, 2024.

[13] Y. Zhu and R. Wang, “内源性硫化氢供体在制备治疗类风湿性关节炎药物中的用途 [Use of an endogenous hydrogen-sulfide donor in preparing a drug for rheumatoid arthritis],” China Patent CN 113181155 A, Jul. 30, 2021.