Nanotherapeutics for the Treatment of Hepatocellular Carcinoma

Recent Patents and Commercially Available Nanotherapeutics on Hepatocellular Carcinoma

Author(s): Susanthi Jayasinghe, Imalka Munaweera, Disni Dedunupitiya, Chamalki Madhusha, Nilwala Kottegoda and Veranja Karunaratne * .

Pp: 449-489 (41)

DOI: 10.2174/9789815039740122010013

* (Excluding Mailing and Handling)

Abstract

Hepatocellular carcinoma (HCC) remains a significant reason for cancerassociated
deaths. The diagnostic methods for early-stage detection are insufficient,
and there are limited treatments available for the late stages. Thus, novel approaches
from nanotechnology have gained much attention to overcome the major hurdles in
designing nanoscale materials that could be used in both diagnosis and treatments.
Recently approved patents showed that progress had been made with nanotechnology
in both diagnosis and therapy. The invention of HCC biomarkers, such as alphafetoprotein,
liver carboxylesterase 1, glypican-3, endoglin, or CD105, has made
significant progress in the area of diagnosis. On the other hand, methods for enhancing
the sensitivity and specificity of imaging in nuclear magnetic resonance using Ga3+ and
nanogold Computed Tomography (CT) contrast agents are noteworthy in the accuracy
of cancer imaging. Nanodrugs have long-circulating times inside the body while
enhancing the bioavailability of these drugs and improving efficacy without higher
doses. Polymer-based nanoparticles, liposomal nanoparticles, and magnetic nano-drug
vehicles are used in therapeutics to transport drugs like paclitaxel, docetaxel,
doxorubicin, and mitomycin. Antisense oligodeoxynucleotides of midkine, phosphoryl
N-fatty acyl nucleosides, siRNAs, and polypeptides have all been used. The long
period between clinical trials and commercialization of nanotherapeutics and key issues
related to clinical development should be addressed by eliminating the regulatory
hurdles limiting nanotherapeutics for HCC in the market.


Keywords: Cancer chemotherapy, Cancer nanotechnology, Clinical trial, Commercial nanotherapeutics, Computed tomography, Diagnosis, Doxorubicin, Drug delivery, EPR effect, FDA, Hepatocellular carcinoma, Liposomes, Liver cancer, Nanoparticles, Nanotherapeutics, Nanomedicine, Nuclear magnetic resonance, Patents, Treatments.

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      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ChapterController.php:1465
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
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      240μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
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      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ChapterController.php:1478
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
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      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1518
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 51833843 and j.to_ip >=51833843 )) and ((j.from_date <= 1739988278 and j.to_date >= 1739988278 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 16550) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 51833843 and j.to_ip >=51833843 )) and ((j.from_date <= 1739988278 and j.to_date >= 1739988278 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 16550) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 51833843 and j.to_ip >=51833843 )) and ((j.from_date <= 1739988278 and j.to_date >= 1739988278 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 16550)
      520μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1549
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` where `b`.`banner_ebook` = 1 and `bd`.`content_type` = 'B' and `bd`.`content_id` = 3312 and `b`.`banner_from_date` <= 1739988278 and `b`.`banner_to_date` >= 1739988278 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.02msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 3312
      • 3: 1739988278
      • 4: 1739988278
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='46bbfb67830c6a853c39e42a48e01488'
      190μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\Keywords
    19Keywords.php#?
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        aemR1ChuFEzpdPyfHDCSdgFvKvk73aQWP5FeuCud
        uc_cart_id
        46bbfb67830c6a853c39e42a48e01488
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/16550" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/16550
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:17 [ "x-https" => array:1 [ 0 => "1" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] "priority" => array:1 [ 0 => "u=0, i" ] "cookie" => array:1 [ 0 => "wayfindertarget=eyJpdiI6ImlQL0tmelpEQnp6UEhBQXU2ckg0U2c9PSIsInZhbHVlIjoidUZDTmlsUlNqYWRtbnppbVRySUZuUVRPOWhWcVBwVEZiL0xQOGNXUUtlWT0iLCJtYWMiOiI3MTg5ZjM5MmVjYTJmY2Y0NzcxMzc2ZWQyODFjMjM3YzNlNTVjNWVkZjYyYjVjZDFiY2ZlZTgxMzdjMzkzY2VmIiwidGFnIjoiIn0%3Dwayfindertarget=eyJpdiI6ImlQL0tmelpEQnp6UEhBQXU2ckg0U2c9PSIsInZhbHVlIjoidUZDTmlsUlNqYWRtbnppbVRySUZuUVRPOWhWcVBwVEZiL0xQOGNXUUtlWT0iLCJtYWMiOiI3MTg5ZjM5MmVjYTJm" ] "accept-encoding" => array:1 [ 0 => "gzip, deflate, br, zstd" ] "sec-fetch-dest" => array:1 [ 0 => "document" ] "sec-fetch-user" => array:1 [ 0 => "?1" ] "sec-fetch-mode" => array:1 [ 0 => "navigate" ] "sec-fetch-site" => array:1 [ 0 => "none" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "sec-ch-ua-platform" => array:1 [ 0 => ""Windows"" ] "sec-ch-ua-mobile" => array:1 [ 0 => "?0" ] "sec-ch-ua" => array:1 [ 0 => ""HeadlessChrome";v="129", "Not=A?Brand";v="8", "Chromium";v="129"" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] ]
        request_cookies
        0 of 0
        array:1 [ "wayfindertarget" => null ]
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Wed, 19 Feb 2025 18:04:38 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6Im9tSFRvdFc2SnBsUElaM1ZWbHpFaGc9PSIsInZhbHVlIjoiQ2tPd2Q0UndjWitjVTYyT1hCUlRKK3Fla09Fdjg4T1cvQ2J3UXNEM2gwZzdPNjFDWStYZkVSZnRXSWNqMWFmOXZheW1SWHpNU0VieWdVeWNzMll3U3lsQ2JvSmQzSW1FU1RSaUJ4dlc3UVdQc1ZReGcxalNtZS9hMGtMNnIxNGMiLCJtYWMiOiIxNjQ2OWZhN2JjZWY0YmNiNWUyODY3YzhjOGU1Y2Q3ODE3ZjBhZWVkYTQ2OTU2YWJmMTUxMGY1NjdkMTk4NGZkIiwidGFnIjoiIn0%3D; expires=Sat, 22 Feb 2025 06:04:38 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6Im9tSFRvdFc2SnBsUElaM1ZWbHpFaGc9PSIsInZhbHVlIjoiQ2tPd2Q0UndjWitjVTYyT1hCUlRKK3Fla09Fdjg4T1cvQ2J3UXNEM2gwZzdPNjFDWStYZkVSZnRXSWNqMWFmOXZheW1SW" 1 => "alphaeurekaselectnet_session=eyJpdiI6IlpHRGJoVExNR0pyWlRPRXBPWWJYcUE9PSIsInZhbHVlIjoiTkNJcU9FcmY3aUxYQjdYWDhRZjVoTGpKY0Z6ZGdrMzBsYXVZeWFibGkxdTFOdC9vY3QwNUJEc09DdGZzYWtQNlR0dEhXQ0Mvbk1LblBkVmhjSk52RkJISFFJU0hmRDhnUHNzbWpzUHh5M3p3eXNQZ3R4dVpuRHhDTDNCSnlFMUoiLCJtYWMiOiIyMTg2NWM4MmQ5ODdiOWM2NzAxZGM4OWJmMzdkYmZiNWJkNDgyOGM5YWU5NDRhZDhmNGQ5ZjExZWFhZWM3ODM3IiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6IlpHRGJoVExNR0pyWlRPRXBPWWJYcUE9PSIsInZhbHVlIjoiTkNJcU9FcmY3aUxYQjdYWDhRZjVoTGpKY0Z6ZGdrMzBsYXVZeWFibGkxdTFOdC9vY3QwNUJEc09" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6Im9tSFRvdFc2SnBsUElaM1ZWbHpFaGc9PSIsInZhbHVlIjoiQ2tPd2Q0UndjWitjVTYyT1hCUlRKK3Fla09Fdjg4T1cvQ2J3UXNEM2gwZzdPNjFDWStYZkVSZnRXSWNqMWFmOXZheW1SWHpNU0VieWdVeWNzMll3U3lsQ2JvSmQzSW1FU1RSaUJ4dlc3UVdQc1ZReGcxalNtZS9hMGtMNnIxNGMiLCJtYWMiOiIxNjQ2OWZhN2JjZWY0YmNiNWUyODY3YzhjOGU1Y2Q3ODE3ZjBhZWVkYTQ2OTU2YWJmMTUxMGY1NjdkMTk4NGZkIiwidGFnIjoiIn0%3D; expires=Sat, 22-Feb-2025 06:04:38 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6Im9tSFRvdFc2SnBsUElaM1ZWbHpFaGc9PSIsInZhbHVlIjoiQ2tPd2Q0UndjWitjVTYyT1hCUlRKK3Fla09Fdjg4T1cvQ2J3UXNEM2gwZzdPNjFDWStYZkVSZnRXSWNqMWFmOXZheW1SW" 1 => "alphaeurekaselectnet_session=eyJpdiI6IlpHRGJoVExNR0pyWlRPRXBPWWJYcUE9PSIsInZhbHVlIjoiTkNJcU9FcmY3aUxYQjdYWDhRZjVoTGpKY0Z6ZGdrMzBsYXVZeWFibGkxdTFOdC9vY3QwNUJEc09DdGZzYWtQNlR0dEhXQ0Mvbk1LblBkVmhjSk52RkJISFFJU0hmRDhnUHNzbWpzUHh5M3p3eXNQZ3R4dVpuRHhDTDNCSnlFMUoiLCJtYWMiOiIyMTg2NWM4MmQ5ODdiOWM2NzAxZGM4OWJmMzdkYmZiNWJkNDgyOGM5YWU5NDRhZDhmNGQ5ZjExZWFhZWM3ODM3IiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6IlpHRGJoVExNR0pyWlRPRXBPWWJYcUE9PSIsInZhbHVlIjoiTkNJcU9FcmY3aUxYQjdYWDhRZjVoTGpKY0Z6ZGdrMzBsYXVZeWFibGkxdTFOdC9vY3QwNUJEc09" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "aemR1ChuFEzpdPyfHDCSdgFvKvk73aQWP5FeuCud" "uc_cart_id" => "46bbfb67830c6a853c39e42a48e01488" "_previous" => array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/16550" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-19 18:04:38GET/chapter/165501121921